Verapamil

Overview

Description
A medication used to treat chest pain, abnormal heart rhythms, and high blood pressure.
Description
A medication used to treat chest pain, abnormal heart rhythms, and high blood pressure.
DrugBank ID
DB00661
Type
Small Molecule
US Approved
YES
Other Approved
YES
Clinical Trials
Phase 0
5
Phase 1
50
Phase 2
17
Phase 3
10
Phase 4
28
Therapeutic Categories
  • Antihypertensive Agents Indicated for Hypertension
  • Calcium Channel Blockers

Identification

Summary

Verapamil is a non-dihydropyridine calcium channel blocker used in the treatment of angina, arrhythmia, and hypertension.

Brand Names
Calan, Isoptin, Tarka, Verelan
Generic Name
Verapamil
DrugBank Accession Number
DB00661
Background

Verapamil is a phenylalkylamine calcium channel blocker used in the treatment of high blood pressure, heart arrhythmias, and angina,19 and was the first calcium channel antagonist to be introduced into therapy in the early 1960s.13 It is a member of the non-dihydropyridine class of calcium channel blockers, which includes drugs like diltiazem and flunarizine, but is chemically unrelated to other cardioactive medications.19 Verapamil is administered as a racemic mixture containing equal amounts of the S- and R-enantiomer, each of which is pharmacologically distinct - the S-enantiomer carries approximately 20-fold greater potency than the R-enantiomer, but is metabolized at a higher rate.5

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 454.6016
Monoisotopic: 454.283157714
Chemical Formula
C27H38N2O4
Synonyms
  • Iproveratril
  • Verapamil
  • Vérapamil
  • Verapamilo
  • Verapamilum
External IDs
  • CP-16,533-1
  • D-365

Pharmacology

Indication

Verapamil is indicated in the treatment of vasopastic (i.e. Prinzmetal's) angina, unstable angina, and chronic stable angina. It is also indicated to treat hypertension, for the prophylaxis of repetitive paroxysmal supraventricular tachycardia, and in combination with digoxin to control ventricular rate in patients with atrial fibrillation or atrial flutter.19 Given intravenously, it is indicated for the treatment of various supraventricular tachyarrhythmias, including rapid conversion to sinus rhythm in patients with supraventricular tachycardia and for temporary control of ventricular rate in patients with atrial fibrillation or atrial flutter.18

Verapamil is commonly used off-label for prophylaxis of cluster headaches.4

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofChronic stable angina pectoris••••••••••••••••••
Prophylaxis ofCluster headache••• •••••
Used in combination to manageHeart rateRegimen in combination with: Digoxin (DB00390), Digitoxin (DB01396)••••••••••••••••••
Treatment ofHigh blood pressure (hypertension)•••••••••••••••••••• •••••••• •••••••• ••••••• ••••••• •••••••• •••••••
Used in combination to manageHypertensionCombination Product in combination with: Trandolapril (DB00519)••••••••••••••••••• •••••••• •••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Verapamil is an L-type calcium channel blocker with antiarrhythmic, antianginal, and antihypertensive activity.19 Immediate-release verapamil has a relatively short duration of action, requiring dosing 3 to 4 times daily,19 but extended-release formulations are available that allow for once-daily dosing.17,22 As verapamil is a negative inotropic medication (i.e. it decreases the strength of myocardial contraction), it should not be used in patients with severe left ventricular dysfunction or hypertrophic cardiomyopathy as the decrease in contractility caused by verapamil may increase the risk of exacerbating these pre-existing conditions.17

Mechanism of action

Verapamil inhibits L-type calcium channels by binding to a specific area of their alpha-1 subunit,17Cav1.2, which is highly expressed on L-type calcium channels in vascular smooth muscle and myocardial tissue where these channels are responsible for the control of peripheral vascular resistance and heart contractility.10 Calcium influx through these channels allows for the propagation of action potentials necessary for the contraction of muscle tissue and the heart's electrical pacemaker activity. Verapamil binds to these channels in a voltage- and frequency-dependent manner, meaning affinity is increased 1) as vascular smooth muscle membrane potential is reduced, and 2) with excessive depolarizing stimulus.17

Verapamil's mechanism of action in the treatment of angina and hypertension is likely due to the mechanism described above. Inhibition of calcium influx prevents the contraction of vascular smooth muscle, causing relaxation/dilation of blood vessels throughout the peripheral circulation - this lowers systemic vascular resistance (i.e. afterload) and thus blood pressure. This reduction in vascular resistance also reduces the force against which the heart must push, decreasing myocardial energy consumption and oxygen requirements and thus alleviating angina.19

Electrical activity through the AV node is responsible for determining heart rate, and this activity is dependent upon calcium influx through L-type calcium channels. By inhibiting these channels and decreasing the influx of calcium, verapamil prolongs the refractory period of the AV node and slows conduction, thereby slowing and controlling the heart rate in patients with arrhythmia.19

Verapamil's mechanism of action in the treatment of cluster headaches is unclear, but is thought to result from an effect on other calcium channels (e.g. N-, P-, Q-, or T-type).4

Verapamil is known to interact with other targets, including other calcium channels,14,15,7,8 potassium channels,6,16,4 and adrenergic receptors.11,12

TargetActionsOrganism
AVoltage-dependent L-type calcium channel subunit alpha-1C
inhibitor
Humans
UVoltage-dependent N-type calcium channel subunit alpha-1B
inhibitor
Humans
UVoltage-dependent P/Q-type calcium channel subunit alpha-1A
inhibitor
Humans
UATP-sensitive inward rectifier potassium channel 11
inhibitor
Humans
UVoltage-dependent T-type calcium channel subunit alpha-1G
inhibitor
Humans
UVoltage-dependent T-type calcium channel subunit alpha-1H
inhibitor
Humans
UVoltage-gated inwardly rectifying potassium channel KCNH2
inhibitor
Humans
USodium-dependent serotonin transporter
unknown
Humans
UAlpha-1A adrenergic receptor
antagonist
Humans
UAlpha-1B adrenergic receptor
antagonist
Humans
UAlpha-1D adrenergic receptor
antagonist
Humans
UVoltage-dependent calcium channel
inhibitor
Humans
UATP-dependent translocase ABCB1
inhibitor
blocker
Humans
Absorption

More than 90% of orally administered verapamil is absorbed - despite this, bioavailability ranges only from 20% to 30% due to rapid biotransformation following first-pass metabolism in the portal circulation.19 Absorption kinetic parameters are largely dependent on the specific formulation of verapamil involved. Immediate-release verapamil reaches peak plasma concentrations (i.e. Tmax) between 1-2 hours following administration,19 whereas sustained-release formulations tend to have a Tmax between 6 - 11 hours.17,22

AUC and Cmax values are similarly dependent upon formulation. Chronic administration of immediate-release verapamil every 6 hours resulted in plasma concentrations between 125 and 400 ng/mL.19 Steady-state AUC0-24h and Cmax values for a sustained-release formulation were 1037 ng∙h/ml and 77.8 ng/mL for the R-isomer and 195 ng∙h/ml and 16.8 ng/mL for the S-isomer, respectively.17

Interestingly, the absorption kinetics of verapamil are highly stereospecific - following oral administration of immediate-release verapamil every 8 hours, the relative systemic availability of the S-enantiomer compared to the R-enantiomer was 13% after a single dose and 18% at steady-state.17

Volume of distribution

Verapamil has a steady-state volume of distribution of approximately 300L for its R-enantiomer and 500L for its S-enantiomer.4

Protein binding

Verapamil is extensively protein-bound in plasma. R-verapamil is 94% bound to serum albumin while S-verapamil is 88% bound. Additionally, R-verapamil is 92% bound to alpha-1 acid glycoprotein and S-verapamil is 86% bound.19

Metabolism

Verapamil is extensively metabolized by the liver, with up to 80% of an administered dose subject to elimination via pre-systemic metabolism - interestingly, this first-pass metabolism appears to clear the S-enantiomer of verapamil much faster than the R-enantiomer.17,9 The remaining parent drug undergoes O-demethylation, N-dealkylation, and N-demethylation to a number of different metabolites via the cytochrome P450 enzyme system.9 Norverapamil, one of the major circulating metabolites, is the result of verapamil's N-demethylation via CYP2C8, CYP3A4, and CYP3A5,9 and carries approximately 20% of the cardiovascular activity of its parent drug.17 The other major pathway involved in verapamil metabolism is N-dealkylation via CYP2C8, CYP3A4, and CYP1A2 to the D-617 metabolite. Both norverapamil and D-617 are further metabolized by other CYP isoenzymes to various secondary metabolites. CYP2D6 and CYP2E1 have also been implicated in the metabolic pathway of verapamil, albeit to a minor extent.9 Minor pathways of verapamil metabolism involve its O-demethylation to D-703 via CYP2C8, CYP2C9, and CYP2C18, and to D-702 via CYP2C9 and CYP2C18.9

Several steps in verapamil's metabolic pathway show stereoselective preference for the S-enantiomer of the given substrate, including the generation of the D-620 metabolite by CYP3A4/5 and the D-617 metabolite by CYP2C8.9

Hover over products below to view reaction partners

Route of elimination

Approximately 70% of an administered dose is excreted as metabolites in the urine and ≥16% in the feces within 5 days. Approximately 3% - 4% is excreted in the urine as unchanged drug.19

Half-life

Single-dose studies of immediate-release verapamil have demonstrated an elimination half-life of 2.8 to 7.4 hours, which increases to 4.5 to 12.0 hours following repetitive dosing.19 The elimination half-life is also prolonged in patients with hepatic insufficiency (14 to 16 hours) and in the elderly (approximately 20 hours).17 Intravenously administered verapamil has rapid distribution phase half-life of approximately 4 minutes, followed by a terminal elimination phase half-life of 2 to 5 hours.18

Clearance

Systemic clearance following 3 weeks of continuous treatment was approximately 340 mL/min for R-verapamil and 664 mL/min for S-verapamil.5 Of note, apparent oral clearance appears to vary significantly between single dose and multiple-dose conditions. The apparent oral clearance following single doses of verapamil was approximately 1007 mL/min for R-verapamil and 5481 mL/min for S-verapamil, whereas 3 weeks of continuous treatment resulted in apparent oral clearance values of approximately 651 mL/min for R-verapamil and 2855 mL/min for S-verapamil.5

Adverse Effects
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Toxicity

Verapamil's reported oral TDLo is 14.4 mg/kg in women and 3.429 mg/kg in men.21 The oral LD50 is 150 mg/kg in rats and 163 mg/kg in mice.21

As there is no antidote for verapamil overdosage, treatment is largely supportive. Symptoms of overdose are generally consistent with verapamil's adverse effect profile (i.e. hypotension, bradycardia, arrhythmia) but instances of non-cardiogenic pulmonary edema have been observed following ingestion of large overdoses (up to 9 grams).17 In acute overdosage, consider the use of gastrointestinal decontamination with cathartics and/or bowel irrigation. Patients presenting with significant myocardial depression may require intravenous calcium, atropine, vasopressors, or other inotropes. Consider the formulation responsible for the overdose prior to treatment - sustained-release formulations may result in delayed pharmacodynamic effects, and these patients should be monitored closely for at least 48 hours following ingestion.17

Pathways
PathwayCategory
Verapamil Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Beta-1 adrenergic receptor---(G;G) / (C;G)G > CEffect Directly StudiedPatients with this genotype require a lower dosage of verapamil to achieve a favourable rate-control response when treating atrial fibrillation.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe metabolism of 1,2-Benzodiazepine can be decreased when combined with Verapamil.
AbacavirVerapamil may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbaloparatideThe risk or severity of adverse effects can be increased when Verapamil is combined with Abaloparatide.
AbametapirThe serum concentration of Verapamil can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Verapamil can be increased when combined with Abatacept.
Food Interactions
  • Avoid alcohol. Verapamil significantly inhibits the elimination of alcohol, leading to elevated blood alcohol levels.
  • Avoid grapefruit products. Co-administration with grapefruit may significantly increase serum concentrations.
  • Take with or without food. Recommendations vary from product to product - consult individual product monographs for additional information.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Verapamil hydrochlorideV3888OEY5R152-11-4DOQPXTMNIUCOSY-UHFFFAOYSA-N
Product Images
International/Other Brands
Bosoptin (Bosnalijek) / Isoptin (Abbott) / Verisop (Gerard) / Vermin (Ratiopharm) / Vermine (Pharmasant) / Verogalid (Ivax) / Verogalid ER (Ivax) / Verpamil (Mylan) / Vertab (Trinity-Chiesi) / Vetrimil (CCPC) / Zolvera (Rosemont)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CalanTablet, film coated80 mg/1OralG.D. Searle LLC Division of Pfizer Inc1984-09-102018-06-30US flag
CalanTablet, film coated40 mg/1OralG.D. Searle LLC2006-06-012006-06-01US flag
CalanTablet, film coated120 mg/1OralG.D. Searle LLC Division of Pfizer Inc1984-09-10Not applicableUS flag
CalanTablet, film coated120 mg/1OralPhysicians Total Care, Inc.1994-07-052012-06-30US flag
Calan SRTablet, film coated, extended release120 mg/1OralPfizer Laboratories Div Pfizer Inc2021-10-252023-07-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Alti-verapamil - 120mgTablet120 mgOralAltimed Pharma Inc.1990-12-312004-08-03Canada flag
Alti-verapamil - 80mgTablet80 mgOralAltimed Pharma Inc.1990-12-312004-08-03Canada flag
Apo-verap SRTablet, extended release240 mgOralApotex Corporation2003-04-24Not applicableCanada flag
Apo-verap SRTablet, extended release180 mgOralApotex Corporation2003-04-24Not applicableCanada flag
Apo-verap SRTablet, extended release120 mgOralApotex Corporation2003-04-24Not applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
TarkaVerapamil hydrochloride (240 mg) + Trandolapril (2 mg)Tablet, extended releaseOralBgp Pharma Ulc2002-07-152019-11-19Canada flag
TarkaVerapamil hydrochloride (240 mg) + Trandolapril (4 mg)Tablet, extended releaseOralBgp Pharma Ulc2002-07-152019-11-19Canada flag
TarkaVerapamil hydrochloride (180 mg/1) + Trandolapril (2 mg/1)Tablet, film coated, extended releaseOralPhysicians Total Care, Inc.2009-01-01Not applicableUS flag
TarkaVerapamil hydrochloride (240 mg/1) + Trandolapril (4 mg/1)Tablet, film coated, extended releaseOralAbbvie1996-10-222021-08-18US flag
TarkaVerapamil hydrochloride (180 mg/1) + Trandolapril (2 mg/1)Tablet, film coated, extended releaseOralAbbvie1996-10-222021-08-14US flag

Categories

ATC Codes
C09BB10 — Trandolapril and verapamilC08DA51 — Verapamil, combinationsC08DA01 — Verapamil
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylbutylamines. These are compounds containing a phenylbutylamine moiety, which consists of a phenyl group substituted at the fourth carbon by an butan-1-amine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylbutylamines
Direct Parent
Phenylbutylamines
Alternative Parents
Dimethoxybenzenes / Phenylpropanes / Phenethylamines / Phenoxy compounds / Anisoles / Aralkylamines / Alkyl aryl ethers / Trialkylamines / Nitriles / Organopnictogen compounds
show 1 more
Substituents
Alkyl aryl ether / Amine / Anisole / Aralkylamine / Aromatic homomonocyclic compound / Carbonitrile / Dimethoxybenzene / Ether / Hydrocarbon derivative / Methoxybenzene
show 14 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary amino compound, aromatic ether, nitrile, polyether (CHEBI:77733)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
CJ0O37KU29
CAS number
52-53-9
InChI Key
SGTNSNPWRIOYBX-UHFFFAOYSA-N
InChI
InChI=1S/C27H38N2O4/c1-20(2)27(19-28,22-10-12-24(31-5)26(18-22)33-7)14-8-15-29(3)16-13-21-9-11-23(30-4)25(17-21)32-6/h9-12,17-18,20H,8,13-16H2,1-7H3
IUPAC Name
2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile
SMILES
COC1=C(OC)C=C(CCN(C)CCCC(C#N)(C(C)C)C2=CC(OC)=C(OC)C=C2)C=C1

References

Synthesis Reference

Philippe Baudier, Arthur De Boeck, Jacques Fossion, "Novel galenic forms of verapamil, their preparation and medicines containing said novel galenic forms." U.S. Patent US4859469, issued April, 1987.

US4859469
General References
  1. Bellamy WT: P-glycoproteins and multidrug resistance. Annu Rev Pharmacol Toxicol. 1996;36:161-83. [Article]
  2. Ahmed JH, Meredith PA, Elliott HL: The influence of age on the pharmacokinetics of verapamil. Pharmacol Res. 1991 Oct;24(3):227-33. doi: 10.1016/1043-6618(91)90085-c. [Article]
  3. Dadashzadeh S, Javadian B, Sadeghian S: The effect of gender on the pharmacokinetics of verapamil and norverapamil in human. Biopharm Drug Dispos. 2006 Oct;27(7):329-34. doi: 10.1002/bdd.512. [Article]
  4. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [Article]
  5. Busse D, Fromm MF, Morike K, Drescher S, Kuhlkamp V, Eichelbaum M: Disposition and pharmacologic effects of R/S-verapamil in patients with chronic atrial fibrillation: an investigation comparing single and multiple dosing. Clin Pharmacol Ther. 2001 May;69(5):324-32. doi: 10.1067/mcp.2001.115125. [Article]
  6. Ninomiya T, Takano M, Haruna T, Kono Y, Horie M: Verapamil, a Ca2+ entry blocker, targets the pore-forming subunit of cardiac type KATP channel (Kir6.2). J Cardiovasc Pharmacol. 2003 Aug;42(2):161-8. doi: 10.1097/00005344-200308000-00002. [Article]
  7. Bergson P, Lipkind G, Lee SP, Duban ME, Hanck DA: Verapamil block of T-type calcium channels. Mol Pharmacol. 2011 Mar;79(3):411-9. doi: 10.1124/mol.110.069492. Epub 2010 Dec 13. [Article]
  8. Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. doi: 10.1124/jpet.108.145672. Epub 2008 Oct 30. [Article]
  9. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  10. Striessnig J, Ortner NJ, Pinggera A: Pharmacology of L-type Calcium Channels: Novel Drugs for Old Targets? Curr Mol Pharmacol. 2015;8(2):110-22. [Article]
  11. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [Article]
  12. Motulsky HJ, Snavely MD, Hughes RJ, Insel PA: Interaction of verapamil and other calcium channel blockers with alpha 1- and alpha 2-adrenergic receptors. Circ Res. 1983 Feb;52(2):226-31. [Article]
  13. Echizen H, Eichelbaum M: Clinical pharmacokinetics of verapamil, nifedipine and diltiazem. Clin Pharmacokinet. 1986 Nov-Dec;11(6):425-49. doi: 10.2165/00003088-198611060-00002. [Article]
  14. Dobrev D, Milde AS, Andreas K, Ravens U: The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum. Br J Pharmacol. 1999 May;127(2):576-82. doi: 10.1038/sj.bjp.0702574. [Article]
  15. Freeze BS, McNulty MM, Hanck DA: State-dependent verapamil block of the cloned human Ca(v)3.1 T-type Ca(2+) channel. Mol Pharmacol. 2006 Aug;70(2):718-26. Epub 2006 May 12. [Article]
  16. Duan JJ, Ma JH, Zhang PH, Wang XP, Zou AR, Tu DN: Verapamil blocks HERG channel by the helix residue Y652 and F656 in the S6 transmembrane domain. Acta Pharmacol Sin. 2007 Jul;28(7):959-67. [Article]
  17. FDA Approved Drug Products: Verelan® PM extended-release capsules [Link]
  18. FDA Approved Drug Products: Verapamil HCl for intravenous injection [Link]
  19. Verapamil FDA Label [Link]
  20. FDA Approved Drugs: Tarka® extended-release tablets [Link]
  21. CaymanChem: Verapamil MSDS [Link]
  22. FDA Approved Drug Products: Calan SR tablets [Link]
Human Metabolome Database
HMDB0001850
KEGG Drug
D02356
KEGG Compound
C07188
PubChem Compound
2520
PubChem Substance
46508158
ChemSpider
2425
BindingDB
81939
RxNav
11170
ChEBI
77733
ChEMBL
CHEMBL6966
Therapeutic Targets Database
DAP000040
PharmGKB
PA451868
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Verapamil

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableCoronary Heart Disease (CHD) / Verapamil Toxicity1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableCoronavirus Disease 2019 (COVID‑19) / COVID / Hypertension1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableErectile Dysfunction1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentArrhythmia / Atrial Fibrillation1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentAtrial Fibrillation1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Mylan pharmaceuticals inc
  • Elan drug delivery inc
  • Gd searle llc
  • Fsc laboratories inc
  • Abraxis pharmaceutical products
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • International medication system
  • Luitpold pharmaceuticals inc
  • Marsam pharmaceuticals llc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Ranbaxy laboratories inc
  • Glenmark generics ltd
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Par pharmaceutical inc
  • Pliva inc
  • Actavis elizabeth llc
  • Heritage pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Sandoz inc
  • Warner chilcott div warner lambert co
  • Watson laboratories inc
Packagers
  • Abbott Laboratories Ltd.
  • Advanced Pharmaceutical Services Inc.
  • Alza Corp.
  • Amerisource Health Services Corp.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • BASF Corp.
  • Cardinal Health
  • Caremark LLC
  • Comprehensive Consultant Services Inc.
  • Copley Chemical Co.
  • Dee Stevens and Son Feeder
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Duramed
  • Elan Pharmaceuticals Inc.
  • FSC Laboratories
  • GD Searle LLC
  • General Injectables and Vaccines Inc.
  • Glenmark Generics Ltd.
  • Golden State Medical Supply Inc.
  • Group Health Cooperative
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Hospira Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacia Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Ranbaxy Laboratories
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Schwarz Pharma Inc.
  • Southwood Pharmaceuticals
  • Talbert Medical Management Corp.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Vangard Labs Inc.
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
TabletOral
Tablet, extended releaseOral180 mg
TabletOral240.000 mg
Capsule180 mg
Capsule240 mg
Capsule, coatedOral240 mg
Solution2.5 mg/mL
Tablet, coatedOral120 mg
Injection, solutionIntravenous125 MG/50ML
Pill80 MG
SolutionIntravenous5 mg/2ml
Solution5 mg/2ml
Tablet, film coatedOral120 MG
Tablet, sugar coatedOral40 mg
Injection, solutionIntravenous5 mg/2ml
Tablet, sugar coatedOral
Tablet, film coatedOral80 MG
Tablet, film coatedOral40 MG
Tablet, film coatedOral240 mg
Tablet, coatedOral120 mg/1
Tablet, coatedOral180 mg/1
Tablet, coatedOral240 mg/1
Tablet, extended releaseOral240 mg
Tablet, film coatedOral240.0 mg
InjectionParenteral5 mg
TabletOral120 mg
Tablet, extended releaseOral120 mg
SolutionParenteral5 mg
TabletOral40 mg
TabletOral80 mg
Tablet, extended releaseOral
Tablet, extended releaseOral
Tablet, film coated, extended releaseOral
Tablet, film coatedOral
Tablet, delayed releaseOral
Capsule, coatedOral
Capsule
TabletOral80.00 mg
CapsuleOral
SolutionIntravenous5.000 mg
Tablet, film coatedOral
Capsule, delayed release
Tablet, coatedOral
Pill
TabletOral240 MG
InjectionIntravenous5 mg/1mL
Capsule, delayed release pelletsOral120 mg/1
Capsule, delayed release pelletsOral180 mg/1
Capsule, extended releaseOral100 mg/1
Capsule, extended releaseOral120 mg/1
Capsule, extended releaseOral180 mg/1
Capsule, extended releaseOral200 mg/1
Capsule, extended releaseOral240 mg/1
Capsule, extended releaseOral300 mg/1
InjectionIntravenous10 mg/4mL
InjectionIntravenous2.5 mg/1mL
InjectionIntravenous5 mg/2mL
Injection, solutionIntravenous2.5 mg/1 mL
Injection, solutionIntravenous2.5 mg/1mL
PowderNot applicable1 kg/1kg
TabletOral120 mg/1
TabletOral180 mg/1
TabletOral240 mg/1
TabletOral40 mg/1
TabletOral80 mg/1
Tablet, extended releaseOral120 mg/1
Tablet, extended releaseOral180 mg/1
Tablet, extended releaseOral240 mg/1
Tablet, film coatedOral120 mg/1
Tablet, film coatedOral40 mg/1
Tablet, film coatedOral80 mg/1
Tablet, film coated, extended releaseOral120 mg/1
Tablet, film coated, extended releaseOral180 mg/1
Tablet, film coated, extended releaseOral240 mg/1
LiquidIntravenous2.5 mg / mL
SolutionIntravenous2.5 mg / mL
Capsule, extended releaseOral
SolutionIntravenous2.50 mg
Tablet, coatedOral12000000 mg
Tablet, coatedOral84 mg
Tablet, film coatedOral81.6 mg
Tablet, coatedOral80 mg
SolutionIntravenous5 mg
Tablet, delayed releaseOral80 mg
Capsule, delayed release pelletsOral240 mg/1
Capsule, delayed release pelletsOral360 mg/1
Capsule, extended releaseOral120 mg
Capsule, extended releaseOral180 mg
Capsule, extended releaseOral240 mg
Injection, solutionIntravenous2.5 mg/mL
InjectionIntravenous2.5 mg/ml
TabletOral80.000 mg
SolutionParenteral250.000 mg
Tablet, coatedOral40 mg
Prices
Unit descriptionCostUnit
Verelan 360 mg 24 Hour Capsule6.82USD capsule
Verelan 360 mg cap pellet6.73USD pellet
Verelan pm 300 mg cap pellet5.87USD pellet
Verelan 240 mg 24 Hour Capsule4.76USD capsule
Verelan 240 mg cap pellet4.58USD pellet
Verelan 180 mg 24 Hour Capsule4.22USD capsule
Verelan 180 mg cap pellet4.06USD pellet
Verelan pm 200 mg cap pellet4.04USD pellet
Verelan 120 mg cap pellet3.87USD pellet
Verapamil HCl CR 300 mg 24 Hour Capsule3.82USD capsule
Isoptin sr 240 mg tablet3.32USD tablet
Verapamil hcl powder3.24USD g
Calan SR 240 mg Controlled Release Tabs3.15USD tab
Isoptin SR 240 mg Controlled Release Tabs3.14USD tab
Verelan pm 100 mg cap pellet3.13USD pellet
Calan sr 240 mg caplet3.09USD caplet
Covera-HS 240 mg 24 Hour tablet3.09USD tablet
Covera-hs 240 mg tablet sa2.97USD tablet
Isoptin sr 180 mg tablet2.9USD tablet
Calan SR 180 mg Controlled Release Tabs2.8USD tab
Isoptin SR 180 mg Controlled Release Tabs2.74USD tab
Calan sr 180 mg caplet2.7USD caplet
Verapamil HCl CR 200 mg 24 Hour Capsule2.62USD capsule
Isoptin sr 120 mg tablet2.29USD tablet
Calan SR 120 mg Controlled Release Tabs2.27USD tab
Covera-HS 180 mg 24 Hour tablet2.2USD tablet
Isoptin SR 120 mg Controlled Release Tabs2.16USD tab
Calan sr 120 mg caplet2.13USD caplet
Covera-hs 180 mg tablet sa2.11USD tablet
Verapamil HCl CR 360 mg 24 Hour Capsule2.1USD capsule
Verapamil HCl CR 100 mg 24 Hour Capsule2.04USD capsule
Isoptin Sr 240 mg Sustained-Release Tablet2.03USD tablet
Calan sr 240 mg caplet sa1.77USD caplet
Verapamil HCl CR 240 mg 24 Hour Capsule1.69USD capsule
Verapamil HCl CR 240 mg Controlled Release Tabs1.6USD tab
Calan 120 mg tablet1.56USD tablet
Isoptin Sr 180 mg Sustained-Release Tablet1.52USD tablet
Verapamil HCl CR 180 mg 24 Hour Capsule1.5USD capsule
Calan sr 180 mg caplet sa1.46USD caplet
Verapamil HCl CR 120 mg 24 Hour Capsule1.43USD capsule
Verapamil HCl CR 180 mg Controlled Release Tabs1.41USD tab
Isoptin Sr 120 mg Sustained-Release Tablet1.34USD tablet
Calan 80 mg tablet1.25USD tablet
Verapamil 2.5 mg/ml vial1.18USD ml
Verapamil HCl CR 120 mg Controlled Release Tabs1.12USD tab
Apo-Verap Sr 240 mg Sustained-Release Tablet0.91USD tablet
Mylan-Verapamil Sr 240 mg Sustained-Release Tablet0.91USD tablet
Novo-Veramil Sr 240 mg Sustained-Release Tablet0.91USD tablet
Pms-Verapamil Sr 240 mg Sustained-Release Tablet0.91USD tablet
Calan 40 mg tablet0.76USD tablet
Apo-Verap Sr 120 mg Sustained-Release Tablet0.72USD tablet
Mylan-Verapamil Sr 120 mg Sustained-Release Tablet0.72USD tablet
Verapamil HCl 120 mg tablet0.71USD tablet
Apo-Verap Sr 180 mg Sustained-Release Tablet0.69USD tablet
Mylan-Verapamil Sr 180 mg Sustained-Release Tablet0.69USD tablet
Verapamil HCl 80 mg tablet0.56USD tablet
Apo-Verap 120 mg Tablet0.45USD tablet
Mylan-Verapamil 120 mg Tablet0.45USD tablet
Nu-Verap 120 mg Tablet0.45USD tablet
Verapamil 120 mg tablet0.39USD tablet
Verapamil 80 mg tablet0.31USD tablet
Verapamil HCl 40 mg tablet0.29USD tablet
Apo-Verap 80 mg Tablet0.29USD tablet
Mylan-Verapamil 80 mg Tablet0.29USD tablet
Nu-Verap 80 mg Tablet0.29USD tablet
Verapamil 40 mg tablet0.28USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5785994No1998-07-282009-10-22US flag
US6096339No2000-08-012017-04-04US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00394 mg/mLALOGPS
logP5.23ALOGPS
logP5.04Chemaxon
logS-5.1ALOGPS
pKa (Strongest Basic)9.68Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area63.95 Å2Chemaxon
Rotatable Bond Count13Chemaxon
Refractivity132.65 m3·mol-1Chemaxon
Polarizability51.7 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9371
Blood Brain Barrier+0.6323
Caco-2 permeable+0.738
P-glycoprotein substrateSubstrate0.7874
P-glycoprotein inhibitor IInhibitor0.9056
P-glycoprotein inhibitor IIInhibitor0.855
Renal organic cation transporterInhibitor0.6259
CYP450 2C9 substrateNon-substrate0.8029
CYP450 2D6 substrateNon-substrate0.8706
CYP450 3A4 substrateSubstrate0.7657
CYP450 1A2 substrateNon-inhibitor0.9553
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9181
Ames testNon AMES toxic0.8393
CarcinogenicityNon-carcinogens0.6463
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.4137 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7687
hERG inhibition (predictor II)Inhibitor0.8188
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0cdu-4391500000-cd36ebd65bc8c7765961
Mass Spectrum (Electron Ionization)MSsplash10-0udi-3519000000-b5e0b9e0caac5cb57222
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-004l-0702900000-6a46ea2d5eed6d8b01eb
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-0006-4109800000-80d342090a0be3344e82
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-054w-0954400000-2def387c7c93ab211423
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, PositiveLC-MS/MSsplash10-0a4i-0000900000-4cde9a4b3a4f83d16afc
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, PositiveLC-MS/MSsplash10-0a4i-0000900000-980b47834e505d54a0e6
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, PositiveLC-MS/MSsplash10-066r-0902800000-ae024239c46b33917426
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, PositiveLC-MS/MSsplash10-014i-0901000000-81d1159b3102cff76218
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, PositiveLC-MS/MSsplash10-014i-0900000000-d9c344fee7b45b4030e6
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , PositiveLC-MS/MSsplash10-0gb9-0914000000-070bdb975910e9aae99c
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , PositiveLC-MS/MSsplash10-03di-0390000000-f41d80462c5d06c4f001
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , PositiveLC-MS/MSsplash10-0097-2980000000-9a2ab0bcab33f7eaac6b
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , PositiveLC-MS/MSsplash10-0uxr-0900000000-252a9989a8511cb2db80
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , PositiveLC-MS/MSsplash10-0f79-0900000000-4fd6ca2c6c19c3bbf8f0
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000900000-4365a47b2dc2f86bb272
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000900000-e6a2b357160bf5b92c22
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-066r-0902400000-d8eac2ccd0a767c7e432
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0901000000-688f3c2345c5d9ccb8a5
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0900000000-cd09f8a2be876936f662
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0918000000-76641dd6dbc5cb05e79a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000900000-05ea95eb1f39b6515212
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-066r-0902600000-a675e624692c25472ce8
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0901000000-70d820628d2613557239
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0gb9-0900000000-e3ca24cf75d574df08a8
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uyi-0900000000-f3a9fa002c56d3e5689a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0zg0-2900000000-101e077b890671063633
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000900000-84b4516ac84e6912cc15
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-066r-0902600000-bc1701c307e45ee4dcd7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0901000000-6fbdab598bcb6147a4bf
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0gb9-0900000000-ce61116806eaa908681c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0900000000-ad3f25e02a7c8e66fb6a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0zgr-2900000000-792b9009086561f6c398
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0918000000-e7a5a3f8c88dc40683fd
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-0000900000-4cde9a4b3a4f83d16afc
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-0000900000-9a5c5240148f82cc6add
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-066r-0902800000-ae024239c46b33917426
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-0901000000-81d1159b3102cff76218
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-0900000000-2411d65dfe09741dde81
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0gb9-0914000000-0463345a8ab0de7aa99e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0900000000-42074ab645b7af0ef79f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0zgi-0900000000-20360f78435d5f482709
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0819000000-7f68ebd6e344adf12101
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0918000000-d3727bbe601b80eabfb3
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0100900000-0a928f78000f291f031d
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-066r-0902600000-40f800e4a364d9ca214c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0gb9-0900000000-4dea228d69d59705fc18
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0500900000-c0bc440571b30d4b5b27
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-066r-0900300000-47a59c15bdbcbc62d6c6
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0ab9-1011900000-1069b9a1ca6cd213f235
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9461300000-a946e3883af52b0d7378
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0021900000-b2bedd2dcc3f0133959c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-1941300000-ef1ad82262f513c09d33
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0umi-0034900000-91a579384abf3d7d9470
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0119300000-c075679051e5a631201a
1H NMR Spectrum1D NMRNot Applicable
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-227.5669678
predicted
DarkChem Lite v0.1.0
[M-H]-212.53043
predicted
DeepCCS 1.0 (2019)
[M+H]+227.2429678
predicted
DarkChem Lite v0.1.0
[M+H]+214.88843
predicted
DeepCCS 1.0 (2019)
[M+Na]+227.7249678
predicted
DarkChem Lite v0.1.0
[M+Na]+221.00804
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:11741969, PubMed:12176756, PubMed:12181424, PubMed:15454078, PubMed:15863612, PubMed:16299511, PubMed:17071743, PubMed:17224476, PubMed:20953164, PubMed:23677916, PubMed:24728418, PubMed:26253506, PubMed:27218670, PubMed:29078335, PubMed:29742403, PubMed:30023270, PubMed:30172029, PubMed:34163037, PubMed:7737988, PubMed:8099908, PubMed:8392192, PubMed:9013606, PubMed:9087614, PubMed:9607315). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm (PubMed:15454078, PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (PubMed:28119464). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable)
Specific Function
alpha-actinin binding
Gene Name
CACNA1C
Uniprot ID
Q13936
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1C
Molecular Weight
248974.1 Da
References
  1. Dilmac N, Hilliard N, Hockerman GH: Molecular determinants of frequency dependence and Ca2+ potentiation of verapamil block in the pore region of Cav1.2. Mol Pharmacol. 2004 Nov;66(5):1236-47. Epub 2004 Jul 30. [Article]
  2. Morel N, Buryi V, Feron O, Gomez JP, Christen MO, Godfraind T: The action of calcium channel blockers on recombinant L-type calcium channel alpha1-subunits. Br J Pharmacol. 1998 Nov;125(5):1005-12. [Article]
  3. Patel MK, Clunn GF, Lymn JS, Austin O, Hughes AD: Effect of serum withdrawal on the contribution of L-type calcium channels (CaV1.2) to intracellular Ca2+ responses and chemotaxis in cultured human vascular smooth muscle cells. Br J Pharmacol. 2005 Jul;145(6):811-7. [Article]
  4. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This alpha-1B subunit gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group. They are involved in pain signaling. Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons. Mediates Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity)
Specific Function
amyloid-beta binding
Gene Name
CACNA1B
Uniprot ID
Q00975
Uniprot Name
Voltage-dependent N-type calcium channel subunit alpha-1B
Molecular Weight
262493.84 Da
References
  1. Dobrev D, Milde AS, Andreas K, Ravens U: The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum. Br J Pharmacol. 1999 May;127(2):576-82. doi: 10.1038/sj.bjp.0702574. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are specifically blocked by the spider omega-agatoxin-IVA (AC P54282) (By similarity). They are however insensitive to dihydropyridines (DHP)
Specific Function
amyloid-beta binding
Gene Name
CACNA1A
Uniprot ID
O00555
Uniprot Name
Voltage-dependent P/Q-type calcium channel subunit alpha-1A
Molecular Weight
282561.605 Da
References
  1. Dobrev D, Milde AS, Andreas K, Ravens U: The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum. Br J Pharmacol. 1999 May;127(2):576-82. doi: 10.1038/sj.bjp.0702574. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium (By similarity). Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation
Specific Function
ankyrin binding
Gene Name
KCNJ11
Uniprot ID
Q14654
Uniprot Name
ATP-sensitive inward rectifier potassium channel 11
Molecular Weight
43525.415 Da
References
  1. Ninomiya T, Takano M, Haruna T, Kono Y, Horie M: Verapamil, a Ca2+ entry blocker, targets the pore-forming subunit of cardiac type KATP channel (Kir6.2). J Cardiovasc Pharmacol. 2003 Aug;42(2):161-8. doi: 10.1097/00005344-200308000-00002. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group and are strongly blocked by mibefradil. A particularity of this type of channel is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
Specific Function
high voltage-gated calcium channel activity
Gene Name
CACNA1G
Uniprot ID
O43497
Uniprot Name
Voltage-dependent T-type calcium channel subunit alpha-1G
Molecular Weight
262468.62 Da
References
  1. Freeze BS, McNulty MM, Hanck DA: State-dependent verapamil block of the cloned human Ca(v)3.1 T-type Ca(2+) channel. Mol Pharmacol. 2006 Aug;70(2):718-26. Epub 2006 May 12. [Article]
  2. Bergson P, Lipkind G, Lee SP, Duban ME, Hanck DA: Verapamil block of T-type calcium channels. Mol Pharmacol. 2011 Mar;79(3):411-9. doi: 10.1124/mol.110.069492. Epub 2010 Dec 13. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-sensitive calcium channel that gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group. A particularity of this type of channel is an opening at quite negative potentials, and a voltage-dependent inactivation (PubMed:27149520, PubMed:9670923, PubMed:9930755). T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle (Probable). They may also be involved in the modulation of firing patterns of neurons (PubMed:15048902). In the adrenal zona glomerulosa, participates in the signaling pathway leading to aldosterone production in response to either AGT/angiotensin II, or hyperkalemia (PubMed:25907736, PubMed:27729216)
Specific Function
high voltage-gated calcium channel activity
Gene Name
CACNA1H
Uniprot ID
O95180
Uniprot Name
Voltage-dependent T-type calcium channel subunit alpha-1H
Molecular Weight
259160.2 Da
References
  1. Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. doi: 10.1124/jpet.108.145672. Epub 2008 Oct 30. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity (PubMed:10219239, PubMed:9230439)
Specific Function
delayed rectifier potassium channel activity
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Voltage-gated inwardly rectifying potassium channel KCNH2
Molecular Weight
126653.52 Da
References
  1. Duan JJ, Ma JH, Zhang PH, Wang XP, Zou AR, Tu DN: Verapamil blocks HERG channel by the helix residue Y652 and F656 in the S6 transmembrane domain. Acta Pharmacol Sin. 2007 Jul;28(7):959-67. [Article]
  2. Schneider J, Hauser R, Andreas JO, Linz K, Jahnel U: Differential effects of human ether-a-go-go-related gene (HERG) blocking agents on QT duration variability in conscious dogs. Eur J Pharmacol. 2005 Apr 4;512(1):53-60. [Article]
  3. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Unknown
General Function
Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Essential for serotonin homeostasis in the central nervous system. In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (By similarity). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes (By similarity). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation (PubMed:17506858, PubMed:18317590). Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied. The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity)
Specific Function
actin filament binding
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [Article]
  2. Brown NL, Sirugue O, Worcel M: The effects of some slow channel blocking drugs on high affinity serotonin uptake by rat brain synaptosomes. Eur J Pharmacol. 1986 Apr 9;123(1):161-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Inhibits receptor activity but shows little competition for binding. Likely an allosteric modulator.
General Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes
Specific Function
alpha1-adrenergic receptor activity
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Inhibits receptor activity but shows little competition for binding. Likely an allosteric modulator.
General Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes
Specific Function
alpha1-adrenergic receptor activity
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
Inhibits receptor activity but shows little competition for binding. Likely an allosteric modulator.
General Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium
Specific Function
alpha1-adrenergic receptor activity
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Regulates channel inactivation kinetics
Specific Function
calcium channel regulator activity

Components:
NameUniProt ID
Voltage-dependent calcium channel gamma-1 subunitQ06432
Voltage-dependent calcium channel gamma-2 subunitQ9Y698
Voltage-dependent calcium channel gamma-3 subunitO60359
Voltage-dependent calcium channel gamma-4 subunitQ9UBN1
Voltage-dependent calcium channel gamma-5 subunitQ9UF02
Voltage-dependent calcium channel gamma-6 subunitQ9BXT2
Voltage-dependent calcium channel gamma-7 subunitP62955
Voltage-dependent calcium channel gamma-8 subunitQ8WXS5
Voltage-dependent calcium channel subunit alpha-2/delta-1P54289
Voltage-dependent calcium channel subunit alpha-2/delta-2Q9NY47
Voltage-dependent calcium channel subunit alpha-2/delta-3Q8IZS8
Voltage-dependent calcium channel subunit alpha-2/delta-4Q7Z3S7
Voltage-dependent L-type calcium channel subunit alpha-1CQ13936
Voltage-dependent L-type calcium channel subunit alpha-1DQ01668
Voltage-dependent L-type calcium channel subunit alpha-1FO60840
Voltage-dependent L-type calcium channel subunit alpha-1SQ13698
Voltage-dependent L-type calcium channel subunit beta-1Q02641
Voltage-dependent L-type calcium channel subunit beta-2Q08289
Voltage-dependent L-type calcium channel subunit beta-3P54284
Voltage-dependent L-type calcium channel subunit beta-4O00305
Voltage-dependent N-type calcium channel subunit alpha-1BQ00975
Voltage-dependent P/Q-type calcium channel subunit alpha-1AO00555
Voltage-dependent R-type calcium channel subunit alpha-1EQ15878
Voltage-dependent T-type calcium channel subunit alpha-1GO43497
Voltage-dependent T-type calcium channel subunit alpha-1HO95180
Voltage-dependent T-type calcium channel subunit alpha-1IQ9P0X4
References
  1. Shima E, Katsube M, Kato T, Kitagawa M, Hato F, Hino M, Takahashi T, Fujita H, Kitagawa S: Calcium channel blockers suppress cytokine-induced activation of human neutrophils. Am J Hypertens. 2008 Jan;21(1):78-84. doi: 10.1038/ajh.2007.13. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Blocker
General Function
Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
ATP-dependent translocase ABCB1
Molecular Weight
141477.255 Da
References
  1. Asakura T, Imai A, Ohkubo-Uraoka N, Kuroda M, Iidaka Y, Uchida K, Shibasaki T, Ohkawa K: Relationship between expression of drug-resistance factors and drug sensitivity in normal human renal proximal tubular epithelial cells in comparison with renal cell carcinoma. Oncol Rep. 2005 Sep;14(3):601-7. [Article]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Wang YH, Jones DR, Hall SD: Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71. doi: 10.1124/dmd.104.001834. Epub 2005 Feb 2. [Article]
  3. Zhou S, Yung Chan S, Cher Goh B, Chan E, Duan W, Huang M, McLeod HL: Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet. 2005;44(3):279-304. doi: 10.2165/00003088-200544030-00005. [Article]
  4. Flockhart Table of Drug Interactions [Link]
  5. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  6. Verapamil FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
Specific Function
aromatase activity
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58406.915 Da
References
  1. Kroemer HK, Gautier JC, Beaune P, Henderson C, Wolf CR, Eichelbaum M: Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7. [Article]
  2. Zhou SF, Yang LP, Zhou ZW, Liu YH, Chan E: Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J. 2009 Sep;11(3):481-94. doi: 10.1208/s12248-009-9127-y. Epub 2009 Jul 10. [Article]
  3. Flockhart Table of Drug Interactions [Link]
  4. Verapamil FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
Specific Function
arachidonic acid epoxygenase activity
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Totah RA, Rettie AE: Cytochrome P450 2C8: substrates, inhibitors, pharmacogenetics, and clinical relevance. Clin Pharmacol Ther. 2005 May;77(5):341-52. doi: 10.1016/j.clpt.2004.12.267. [Article]
  2. Busse D, Cosme J, Beaune P, Kroemer HK, Eichelbaum M: Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21. doi: 10.1007/bf00168924. [Article]
  3. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
  4. Verapamil FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
  3. Verapamil FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in retinoid metabolism. Hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may modulate atRA signaling and clearance. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase)
Specific Function
arachidonic acid epoxygenase activity
Gene Name
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
  2. Verapamil FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
Specific Function
aromatase activity
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Wang YH, Jones DR, Hall SD: Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71. doi: 10.1124/dmd.104.001834. Epub 2005 Feb 2. [Article]
  2. Langaee TY, Gong Y, Yarandi HN, Katz DA, Cooper-DeHoff RM, Pepine CJ, Johnson JA: Association of CYP3A5 polymorphisms with hypertension and antihypertensive response to verapamil. Clin Pharmacol Ther. 2007 Mar;81(3):386-91. doi: 10.1038/sj.clpt.6100090. [Article]
  3. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Activator
General Function
A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55944.565 Da
References
  1. Busse D, Cosme J, Beaune P, Kroemer HK, Eichelbaum M: Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21. doi: 10.1007/bf00168924. [Article]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
Specific Function
4-nitrophenol 2-monooxygenase activity
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function
antioxidant activity
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: Verelan® PM extended-release capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
Specific Function
Not Available
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23539.43 Da
References
  1. FDA Approved Drug Products: Verelan® PM extended-release capsules [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
ATP-dependent translocase ABCB1
Molecular Weight
141477.255 Da
References
  1. Tfelt-Hansen P, Tfelt-Hansen J: Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x. [Article]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  3. Verapamil FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
Specific Function
(R)-carnitine transmembrane transporter activity
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Cho SK, Kim CO, Park ES, Chung JY: Verapamil decreases the glucose-lowering effect of metformin in healthy volunteers. Br J Clin Pharmacol. 2014 Dec;78(6):1426-32. doi: 10.1111/bcp.12476. [Article]
  2. Boxberger KH, Hagenbuch B, Lampe JN: Common drugs inhibit human organic cation transporter 1 (OCT1)-mediated neurotransmitter uptake. Drug Metab Dispos. 2014 Jun;42(6):990-5. doi: 10.1124/dmd.113.055095. Epub 2014 Mar 31. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations (PubMed:10215651, PubMed:15107849, PubMed:15795384, PubMed:16729965, PubMed:20601551, PubMed:22206629, PubMed:22569296, PubMed:29530864). Functions as a Na(+)-dependent and pH-dependent high affinity microbial symporter of potent food-derived antioxidant ergothioeine (PubMed:15795384, PubMed:29530864, PubMed:33124720). Transports one sodium ion with one ergothioeine molecule (By similarity). Involved in the absorption of ergothioneine from the luminal/apical side of the small intestine and renal tubular cells, and into non-parenchymal liver cells, thereby contributing to maintain steady-state ergothioneine level in the body (PubMed:20601551). Also mediates the bidirectional transport of acetycholine, although the exact transport mechanism has not been fully identified yet (PubMed:22206629). Most likely exports anti-inflammatory acetylcholine in non-neuronal tissues, thereby contributing to the non-neuronal cholinergic system (PubMed:22206629, PubMed:22569296). Displays a general physiological role linked to better survival by controlling inflammation and oxidative stress, which may be related to ergothioneine and acetycholine transports (PubMed:15795384, PubMed:22206629). May also function as a low-affinity Na(+)-dependent transporter of L-carnitine through the mitochondrial membrane, thereby maintaining intracellular carnitine homeostasis (PubMed:10215651, PubMed:15107849, PubMed:16729965). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (PubMed:35307651)
Specific Function
acetylcholine transmembrane transporter activity
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine (PubMed:10454528, PubMed:10525100, PubMed:10966938, PubMed:17509700, PubMed:20722056, PubMed:33124720). Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 11.3 (PubMed:10454528, PubMed:10525100, PubMed:10966938). In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from Bacillus Subtilis wich induces cytoprotective heat shock proteins contributing to intestinal homeostasis (PubMed:18005709). May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
(R)-carnitine transmembrane transporter activity
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Organic cation/carnitine transporter 2
Molecular Weight
62751.08 Da
References
  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [Article]
  2. Ohashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001 Feb;59(2):358-66. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes (PubMed:10359813, PubMed:11581266, PubMed:15083066). Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (PubMed:11581266, PubMed:15083066). Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells (PubMed:10359813, PubMed:11581266)
Specific Function
ABC-type bile acid transporter activity
Gene Name
ABCC3
Uniprot ID
O15438
Uniprot Name
ATP-binding cassette sub-family C member 3
Molecular Weight
169341.14 Da
References
  1. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Oostendorp RL, van de Steeg E, van der Kruijssen CM, Beijnen JH, Kenworthy KE, Schinkel AH, Schellens JH: Organic anion-transporting polypeptide 1B1 mediates transport of Gimatecan and BNP1350 and can be inhibited by several classic ATP-binding cassette (ABC) B1 and/or ABCG2 inhibitors. Drug Metab Dispos. 2009 Apr;37(4):917-23. doi: 10.1124/dmd.108.024901. Epub 2009 Jan 12. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), at the plasmam membrane (PubMed:19129463, PubMed:7557095). Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) (PubMed:11159893, PubMed:12568656, PubMed:19129463, PubMed:23918469, PubMed:25560245, PubMed:9539145). Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision (PubMed:25560245). Involved in the uptake of clinically used drugs (PubMed:17301733, PubMed:20686826, PubMed:27777271). Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) (PubMed:19129463, PubMed:20358049). Also transports prostaglandin E2 (PubMed:19129463). Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595). Hydrolyzes ATP with low efficiency (PubMed:16230346). Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (PubMed:17050692). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthezing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export (PubMed:36070769). Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway (PubMed:36070769)
Specific Function
ABC-type glutathione S-conjugate transporter activity
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Perrotton T, Trompier D, Chang XB, Di Pietro A, Baubichon-Cortay H: (R)- and (S)-verapamil differentially modulate the multidrug-resistant protein MRP1. J Biol Chem. 2007 Oct 26;282(43):31542-8. doi: 10.1074/jbc.M703964200. Epub 2007 Jul 22. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685)
Specific Function
15-hydroxyprostaglandin dehydrogenase (NAD+) activity
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
ATP-binding cassette sub-family C member 4
Molecular Weight
149525.33 Da
References
  1. Chen ZS, Lee K, Walther S, Raftogianis RB, Kuwano M, Zeng H, Kruh GD: Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50. [Article]
  2. Bai J, Lai L, Yeo HC, Goh BC, Tan TM: Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Lipophilic anion transporter that mediates ATP-dependent transport of glucuronide conjugates such as estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (PubMed:12527806, PubMed:15256465). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Mediates multidrug resistance (MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor drugs, such as, docetaxel and paclitaxel (PubMed:15256465, PubMed:23087055). Does not transport glycocholic acid, taurocholic acid, MTX, folic acid, cAMP, or cGMP (PubMed:12527806)
Specific Function
ABC-type glutathione S-conjugate transporter activity
Gene Name
ABCC10
Uniprot ID
Q5T3U5
Uniprot Name
ATP-binding cassette sub-family C member 10
Molecular Weight
161627.375 Da
References
  1. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:16330770, PubMed:17509534). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
antiporter activity
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Radchenko M, Symersky J, Nie R, Lu M: Structural basis for the blockade of MATE multidrug efflux pumps. Nat Commun. 2015 Aug 6;6:7995. doi: 10.1038/ncomms8995. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate. Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
Specific Function
antiporter activity
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. Radchenko M, Symersky J, Nie R, Lu M: Structural basis for the blockade of MATE multidrug efflux pumps. Nat Commun. 2015 Aug 6;6:7995. doi: 10.1038/ncomms8995. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 06, 2024 19:59