Isradipine

Identification

Summary

Isradipine is a dihydropyridine calcium channel blocker used for the treatment of hypertension.

Generic Name
Isradipine
DrugBank Accession Number
DB00270
Background

Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. It is structurally related to felodipine, nifedipine, and nimodipine and is the most potent calcium-channel blocking agent of the DHP class. Isradipine binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and arterial smooth muscle cells. It exhibits greater selectivity towards arterial smooth muscle cells owing to alternative splicing of the alpha-1 subunit of the channel and increased prevalence of inactive channels in smooth muscle cells. Isradipine may be used to treat mild to moderate essential hypertension.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 371.3871
Monoisotopic: 371.148120797
Chemical Formula
C19H21N3O5
Synonyms
  • Isradipine
  • Isradipino
  • Isradipinum

Pharmacology

Indication

For the management of mild to moderate essential hypertension. It may be used alone or concurrently with thiazide-type diuretics.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofHypertension••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Isradipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of isradipine result in an overall decrease in blood pressure.

Mechanism of action

Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, isradipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives isradipine additional arterial selectivity. At therapeutic sub-toxic concentrations, isradipine has little effect on cardiac myocytes and conduction cells.

TargetActionsOrganism
AVoltage-dependent L-type calcium channel subunit alpha-1C
inhibitor
Humans
AVoltage-dependent calcium channel subunit alpha-2/delta-1
inhibitor
Humans
AVoltage-dependent L-type calcium channel subunit beta-2
inhibitor
Humans
AVoltage-dependent T-type calcium channel subunit alpha-1H
inhibitor
Humans
AVoltage-dependent calcium channel subunit alpha-2/delta-2
inhibitor
Humans
AVoltage-dependent L-type calcium channel subunit alpha-1D
inhibitor
Humans
AVoltage-dependent L-type calcium channel subunit alpha-1S
inhibitor
Humans
Absorption

Isradipine is 90%-95% absorbed and is subject to extensive first-pass metabolism, resulting in a bioavailability of about 15%-24%.

Volume of distribution

Not Available

Protein binding

95%

Metabolism

Hepatic. Completely metabolized prior to excretion and no unchanged drug is detected in the urine.

Route of elimination

Approximately 60% to 65% of an administered dose is excreted in the urine and 25% to 30% in the feces.

Half-life

8 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Symptoms of overdose include lethargy, sinus tachycardia, and transient hypotension. Significant lethality was observed in mice given oral doses of over 200 mg/kg and rabbits given about 50 mg/kg of isradipine. Rats tolerated doses of over 2000 mg/kg without effects on survival.

Pathways
PathwayCategory
Isradipine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

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 Isradipine.
AbacavirIsradipine 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 Isradipine is combined with Abaloparatide.
AbametapirThe serum concentration of Isradipine can be increased when it is combined with Abametapir.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Isradipine.
Food Interactions
  • Take with or without food.

Products

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Product Images
International/Other Brands
Clivoten (Italfarmaco (Italy)) / Esradin (Sigma-Tau (Italy)) / Lomir (Novartis (Austria, Brazil, Czech Republic, Denmark, Finland, Germany, Greece, Hungary, Netherlands, Norway, Poland, Russia, Sweden), Sankyo (Belgium, Italy), Daiichi Sankyo (Portugal, Switzerland), Mizar (Spain)) / Prescal (Novartis (United Kingdom))
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DynaCircTablet, film coated, extended release10 mg/1OralGlaxosmithkline Inc2007-03-012011-09-30US flag
DynaCircCapsule2.5 mg/1OralPhysicians Total Care, Inc.1999-03-042011-05-31US flag
DynaCircTablet, film coated, extended release5 mg/1OralGlaxosmithkline Inc2007-03-012011-10-31US flag
DynaCircCapsule5 mg/1OralGlaxosmithkline Inc2007-03-012010-01-01US flag
DynaCircCapsule2.5 mg/1OralGlaxosmithkline Inc2007-03-012010-01-01US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IsradipineCapsule2.5 mg/1OralElite Laboratories, Inc.2022-12-28Not applicableUS flag
IsradipineCapsule5 mg/1OralActavis Totowa LLC2006-09-012008-08-20US flag
IsradipineCapsule5 mg/1OralGolden State Medical Supply, Inc.2006-04-24Not applicableUS flag
IsradipineCapsule2.5 mg/1OralAvPAK2014-01-062020-01-31US flag
IsradipineCapsule5 mg/1OralEpic Pharma, LLC2021-03-15Not applicableUS flag

Categories

ATC Codes
C08CA03 — Isradipine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzoxadiazoles. These are organic compounds containing a benzene fused to an oxadiazole ring (a five-membered ring with two carbon atoms, one nitrogen atom, and one oxygen atom).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzoxadiazoles
Sub Class
Not Available
Direct Parent
Benzoxadiazoles
Alternative Parents
Dihydropyridinecarboxylic acids and derivatives / Benzenoids / Dicarboxylic acids and derivatives / Vinylogous amides / Enoate esters / Furazans / Heteroaromatic compounds / Methyl esters / Amino acids and derivatives / Enamines
show 6 more
Substituents
Alpha,beta-unsaturated carboxylic ester / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Benzoxadiazole / Carbonyl group / Carboxylic acid derivative
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
YO1UK1S598
CAS number
75695-93-1
InChI Key
HMJIYCCIJYRONP-UHFFFAOYSA-N
InChI
InChI=1S/C19H21N3O5/c1-9(2)26-19(24)15-11(4)20-10(3)14(18(23)25-5)16(15)12-7-6-8-13-17(12)22-27-21-13/h6-9,16,20H,1-5H3
IUPAC Name
3-methyl 5-propan-2-yl 4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
SMILES
COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC2=NON=C12)C(=O)OC(C)C

References

General References
  1. Fletcher H, Roberts G, Mullings A, Forrester T: An open trial comparing isradipine with hydralazine and methyl dopa in the treatment of patients with severe pre-eclampsia. J Obstet Gynaecol. 1999 May;19(3):235-8. [Article]
  2. Ganz M, Mokabberi R, Sica DA: Comparison of blood pressure control with amlodipine and controlled-release isradipine: an open-label, drug substitution study. J Clin Hypertens (Greenwich). 2005 Apr;7(4 Suppl 1):27-31. [Article]
  3. Hattori T, Wang PL: Calcium antagonist isradipine-induced calcium influx through nonselective cation channels in human gingival fibroblasts. Eur J Med Res. 2006 Mar 27;11(3):93-6. [Article]
  4. Johnson BA, Roache JD, Ait-Daoud N, Wallace C, Wells L, Dawes M, Wang Y: Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects. Int J Neuropsychopharmacol. 2005 Jun;8(2):203-13. [Article]
Human Metabolome Database
HMDB0014415
KEGG Drug
D00349
PubChem Compound
3784
PubChem Substance
46505034
ChemSpider
3652
BindingDB
50436176
RxNav
33910
ChEBI
6073
ChEMBL
CHEMBL1648
Therapeutic Targets Database
DAP000134
PharmGKB
PA450131
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Isradipine
MSDS
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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 AvailableCoronavirus Disease 2019 (COVID‑19) / COVID / Hypertension1somestatusstop reasonjust information to hide
Not AvailableCompletedSupportive CareSchizoaffective Disorders / Schizophrenia1somestatusstop reasonjust information to hide
Not AvailableUnknown StatusBasic ScienceSpinal Cord Injury, Chronic1somestatusstop reasonjust information to hide
3CompletedTreatmentParkinson's Disease (PD)1somestatusstop reasonjust information to hide
2CompletedTreatmentParkinson's Disease (PD)2somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Smithkline beecham corp dba glaxosmithkline
  • Actavis totowa llc
  • Watson laboratories inc
  • Glaxosmithkline llc
Packagers
  • Actavis Group
  • Alza Corp.
  • Amerisource Health Services Corp.
  • Caremark LLC
  • Cobalt Pharmaceuticals Inc.
  • GlaxoSmithKline Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Novartis AG
  • Patheon Inc.
  • Pharmaceutical Manufacturing Research Services Inc.
  • Physicians Total Care Inc.
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
TabletOral2.5 mg
CapsuleOral2.5 mg/1
CapsuleOral5 mg/1
Tablet, film coated, extended releaseOral10 mg/1
Tablet, film coated, extended releaseOral5 mg/1
TabletOral0.0025 g
Capsule, coatedOral5 mg
Capsule, extended releaseOral
CapsuleOral2.5 MG
Capsule, extended releaseOral5 MG
Capsule, extended releaseOral2.5 mg
Prices
Unit descriptionCostUnit
DynaCirc CR 10 mg 24 Hour tablet5.59USD tablet
Dynacirc cr 10 mg tablet4.41USD tablet
DynaCirc CR 5 mg 24 Hour tablet3.0USD tablet
Dynacirc cr 5 mg tablet2.88USD tablet
DynaCirc 5 mg capsule2.31USD capsule
Isradipine 5 mg capsule2.0USD capsule
DynaCirc 2.5 mg capsule1.59USD capsule
Isradipine 2.5 mg capsule1.39USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)168-170 °CNot Available
water solubilityPractically insoluble (< 10 mg/L at 37 °C)Not Available
logP4.28SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.228 mg/mLALOGPS
logP3ALOGPS
logP2Chemaxon
logS-3.2ALOGPS
pKa (Strongest Acidic)16.95Chemaxon
pKa (Strongest Basic)-3.3Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area103.55 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity100.08 m3·mol-1Chemaxon
Polarizability37.34 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9965
Blood Brain Barrier-0.8439
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.5855
P-glycoprotein inhibitor IInhibitor0.9322
P-glycoprotein inhibitor IIInhibitor0.8669
Renal organic cation transporterNon-inhibitor0.884
CYP450 2C9 substrateNon-substrate0.8522
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6631
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8557
Ames testNon AMES toxic0.5158
CarcinogenicityNon-carcinogens0.8043
BiodegradationNot ready biodegradable0.9747
Rat acute toxicity2.3960 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8699
hERG inhibition (predictor II)Non-inhibitor0.6895
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-MSsplash10-0006-6059000000-e9ec514baf6b881462eb
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0006-0009000000-3c8fe8c9d5e94c018299
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-03dl-2589000000-e01ef029445c948c93e7
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-0009000000-3c8fe8c9d5e94c018299
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03dl-2589000000-e01ef029445c948c93e7
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0229-0019000000-74b13c1ea3307fdd3d03
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0019000000-288478640551ad735ac4
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-001j-0098000000-aebdf8eca1317e2d599a
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0il0-1097000000-dfe38fd3371b6312551d
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-002g-0491000000-ce8f377088d9bdc41e69
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0ffx-1294000000-1296fc6ca04ea25410e6
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-189.7556572
predicted
DarkChem Lite v0.1.0
[M-H]-184.51237
predicted
DeepCCS 1.0 (2019)
[M+H]+190.4361572
predicted
DarkChem Lite v0.1.0
[M+H]+186.87038
predicted
DeepCCS 1.0 (2019)
[M+Na]+190.4851572
predicted
DarkChem Lite v0.1.0
[M+Na]+194.17455
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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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. Berjukow S, Marksteiner R, Gapp F, Sinnegger MJ, Hering S: Molecular mechanism of calcium channel block by isradipine. Role of a drug-induced inactivated channel conformation. J Biol Chem. 2000 Jul 21;275(29):22114-20. [Article]
  2. Hitzl M, Striessnig J, Neuhuber B, Flucher BE: A mutation in the beta interaction domain of the Ca(2+) channel alpha(1C) subunit reduces the affinity of the (+)-[(3)H]isradipine binding site. FEBS Lett. 2002 Jul 31;524(1-3):188-92. [Article]
  3. Zuhlke RD, Bouron A, Soldatov NM, Reuter H: Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human alpha1C subunit gene. FEBS Lett. 1998 May 8;427(2):220-4. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel (PubMed:35293990). Plays an important role in excitation-contraction coupling (By similarity)
Specific Function
metal ion binding
Gene Name
CACNA2D1
Uniprot ID
P54289
Uniprot Name
Voltage-dependent calcium channel subunit alpha-2/delta-1
Molecular Weight
124566.93 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current (By similarity). Plays a role in shifting voltage dependencies of activation and inactivation of the channel (By similarity). May modulate G protein inhibition (By similarity). May contribute to beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force (PubMed:36424916). Involved in membrane targeting of the alpha-1 subunit CACNA1C (PubMed:17525370)
Specific Function
actin filament binding
Gene Name
CACNB2
Uniprot ID
Q08289
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-2
Molecular Weight
73579.925 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
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. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [Article]
  2. 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
Yes
Actions
Inhibitor
General Function
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G) (PubMed:15111129, PubMed:23339110). Overexpression induces apoptosis
Specific Function
metal ion binding
Gene Name
CACNA2D2
Uniprot ID
Q9NY47
Uniprot Name
Voltage-dependent calcium channel subunit alpha-2/delta-2
Molecular Weight
129816.095 Da
References
  1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [Article]
  2. 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
Yes
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-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines
Specific Function
alpha-actinin binding
Gene Name
CACNA1D
Uniprot ID
Q01668
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1D
Molecular Weight
245138.75 Da
References
  1. Koschak A, Reimer D, Huber I, Grabner M, Glossmann H, Engel J, Striessnig J: alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages. J Biol Chem. 2001 Jun 22;276(25):22100-6. Epub 2001 Apr 2. [Article]
  2. Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J: Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol. 2009 Feb;75(2):407-14. doi: 10.1124/mol.108.049981. Epub 2008 Nov 24. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcoplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group
Specific Function
calmodulin binding
Gene Name
CACNA1S
Uniprot ID
Q13698
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1S
Molecular Weight
212348.1 Da
References
  1. Peterson BZ, Catterall WA: Allosteric interactions required for high-affinity binding of dihydropyridine antagonists to Ca(V)1.1 Channels are modulated by calcium in the pore. Mol Pharmacol. 2006 Aug;70(2):667-75. Epub 2006 May 4. [Article]

Enzymes

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. Michalets EL: Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy. 1998 Jan-Feb;18(1):84-112. [Article]
  2. Get to Know an Enzyme: CYP3A4 Substrates [Link]
  3. Supercyp table [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
Specific Function
ABC-type bile acid transporter activity
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 03, 2024 03:52