Doxazosin

Identification

Summary

Doxazosin is an alpha-1 adrenergic receptor used to treat mild to moderate hypertension and urinary obstruction due to benign prostatic hyperplasia.

Brand Names
Cardura
Generic Name
Doxazosin
DrugBank Accession Number
DB00590
Background

Doxazosin is an alpha-1 antagonist used for the treatment of benign prostatic hypertrophy (BPH) symptoms and hypertension. Other members of this drug class include Prazosin, Terazosin, Tamsulosin, and Alfuzosin.8 Because of its long-lasting effects, doxazosin can be administered once a day.5 It is marketed by Pfizer and was initially approved by the FDA in 1990.20

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 451.4751
Monoisotopic: 451.185568935
Chemical Formula
C23H25N5O5
Synonyms
  • 1-(4-Amino-6,7-dimethoxy-2-chinazolinyl)-4-(2,3-dihydro-1,4-benzodioxixin-2-ylcarbonyl)piperazin
  • 1-(4-Amino-6,7-Dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl)piperazin
  • Doxazosin
  • Doxazosina
  • Doxazosine
  • Doxazosinum

Pharmacology

Indication

Doxazosin is indicated to treat the symptoms of benign prostatic hypertrophy, which may include urinary frequency, urgency, and nocturia, among other symptoms. In addition, doxazosin is indicated alone or in combination with various antihypertensive agents for the management of hypertension.19 Off-label uses of doxazosin include the treatment of pediatric hypertension2 and the treatment of ureteric calculi.3

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Symptomatic treatment ofBenign prostatic hyperplasia (bph)••••••••••••••••••• ••••••• •••••••• •••••••
Treatment ofHypertension••••••••••••••••••
Treatment ofUreteric calculus••• •••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Doxazosin decreases standing and supine blood pressure5 and relieves the symptoms of benign prostatic hypertrophy through the inhibition of alpha-1 receptors. Doxazosin may cause hypotension due to its pharmacological actions. This frequently occurs in the upright position, leading to a feeling of dizziness or lightheadedness. The first dose of doxazosin may lead to such effects, however, subsequent doses may also cause them. The risk of these effects is particularly high when dose adjustments occur or there are long intervals between doxazosin doses. Treatment should be started with the 1 mg dose of doxazosin, followed by slow titration to the appropriate dose.19 Patients must be advised of this risk and to avoid situations in which syncope and dizziness could be hazardous following the ingestion of doxazosin.19 Interestingly doxazosin exerts beneficial effects on plasma lipids. It reduces LDL (low-density lipoprotein) cholesterol and triglyceride levels and increases HDL (high-density lipoprotein) cholesterol levels.5

A note on priapism risk

In rare cases, doxazosin and other alpha-1 blockers may cause priapism, a painful occurrence of persistent and unrelievable penile erection that can lead to impotence if medical attention is not sought as soon as possible. Patients must be advised of the priapism risk associated with doxazosin and to seek medical attention immediately if it is suspected.9,19

Mechanism of action

Doxazosin selectively inhibits the postsynaptic alpha-1 receptors on vascular smooth muscle by nonselectively blocking the alpha-1a, alpha-1b, and alpha-1d subtypes12,13. This action on blood vessels decreases systemic peripheral vascular resistance, reducing blood pressure, exerting minimal effects on the heart rate due to its receptor selectivity.5,10 Norepinephrine-activated alpha-1 receptors located on the prostate gland and bladder neck normally cause contraction of regional muscular tissue, obstructing urinary flow and contributing to the symptoms of benign prostatic hypertrophy. Alpha-1 antagonism causes smooth muscle relaxation in the prostate and bladder, effectively relieving urinary frequency, urgency, weak urinary stream, and other unpleasant effects of BPH.6 Recently, doxazosin was found to cause apoptosis of hERG potassium channels in an in vitro setting, possibly contributing to a risk of heart failure with doxazosin use.14,15,16

TargetActionsOrganism
AAlpha-1A adrenergic receptor
antagonist
Humans
AAlpha-1D adrenergic receptor
antagonist
Humans
UHERG human cardiac K+ channel
inhibitor
Humans
UAlpha-1B adrenergic receptorNot AvailableHumans
Absorption

Doxazosin is rapidly absorbed in the gastrointestinal tract and peak concentrations are achieved within 2-3 hours after administration.11 The bioavailability is about 60%-70%.7,19 The intake of food with doxazosin is not expected to cause clinically significant effects.19

Volume of distribution

The volume of distribution of doxazosin is 1.0-1.9 L/kg.7,11 In a study of radiolabeled doxazosin administered to pregnant rats, doxazosin was found to cross the placenta.19

Protein binding

The plasma protein binding of doxazosin is estimated at 98%.4,19. It has also been shown to be bound to the alpha-1 acid glycoprotein.18

Metabolism

Hepatic metabolism of doxazosin produces inactive O-demethylated and C-hydroxylated metabolites. Metabolism occurs via O-demethylation of the quinazoline nucleus of doxazosin or via hydroxylation of its benzodioxan portion.19 The enzymes involved in the metabolism of doxazosin include CYP2C1923, CYP2D6, CYP2C19, and CYP3A4, which is the primary metabolizing enzyme.22 Doxazosin itself is considered to be mainly responsible for its pharmacological action7, however, some active metabolites have been identified whose pharmacokinetics have not been adequately characterized.19

Hover over products below to view reaction partners

Route of elimination

In a pharmacokinetic study using a 1 mg IV radiolabeled dose and a 2 mg oral dose, 63% of the ingested doxazosin was found to be excreted in the feces and about 9% of the dose was found to be excreted in the urine.7,19 Traces of radiolabeled unchanged drug were found in the urine and about 5% of the administered drug was found as unchanged drug excreted in the feces.19

Half-life

The terminal elimination half-life of doxazosin has been estimated at 9-12 hours according to some resources.4,7 The FDA label indicates the elimination half-life of doxazosin is 22 hours.19

Clearance

The clearance of doxazosin is low and ranges from approximately 1-2 ml/min/kg.4,11

Adverse Effects
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Toxicity

LD50 information

The oral LD50 of doxazosin in mice is >1000 mg/kg.21

Overdose information

Symptoms of overdose include hypotension, changes in heart rate, and drowsiness.10 Administer supportive treatment in case of an overdose with doxazosin. Remove unabsorbed doxazosin from the gastrointestinal tract, correct hypotension, and closely monitor vital signs.10

Pathways
Not Available
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
AbaloparatideThe risk or severity of adverse effects can be increased when Doxazosin is combined with Abaloparatide.
AbametapirThe serum concentration of Doxazosin can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Doxazosin can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Doxazosin.
AbirateroneThe metabolism of Doxazosin can be decreased when combined with Abiraterone.
Food Interactions
  • Avoid alcohol.
  • Take with or without food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Doxazosin mesylate86P6PQK0MU77883-43-3VJECBOKJABCYMF-UHFFFAOYSA-N
Product Images
International/Other Brands
Alfadil (Pfizer (Sweden)) / Cardenalin (Pfizer (Japan; discontinued)) / Cardular (Pfizer (Germany)) / Cardura-1 (Pfizer (Canada)) / Cardura-2 (Pfizer (Canada)) / Cardura-4 (Pfizer (Canada)) / Carduran (Pfizer (Brazil, Denmark, Norway, Spain)) / Diblocin (AstraZeneca (Germany)) / Normothen (Bioindustria (Italy)) / Supressin (Pfizer (Austria))
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CarduraTablet2 mg/1OralRoerig2021-10-19Not applicableUS flag
CarduraTablet4 mg/1OralPhysicians Total Care, Inc.1993-06-222012-07-16US flag
CarduraTablet4 mg/1OralRoerig1991-01-012022-04-30US flag
CarduraTablet8 mg/1OralRoerig2023-02-15Not applicableUS flag
CarduraTablet1 mg/1OralRoerig2021-10-19Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-doxazosinTablet2 mg / tabOralApotex Corporation1999-07-22Not applicableCanada flag
Apo-doxazosinTablet1 mg / tabOralApotex Corporation1999-07-22Not applicableCanada flag
Apo-doxazosinTablet4 mg / tabOralApotex Corporation1999-07-22Not applicableCanada flag
Dom-doxazosinTablet1 mgOralDominion Pharmacal2004-05-26Not applicableCanada flag
Dom-doxazosinTablet4 mgOralDominion Pharmacal2004-05-26Not applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Cardura-1,2,and 4Doxazosin mesylate (1 mg) + Doxazosin mesylate (2 mg) + Doxazosin mesylate (4 mg)Kit; TabletOralAstrazeneca AbNot applicableNot applicableCanada flag
Cardura-1,2,and 4Doxazosin mesylate (1 mg) + Doxazosin mesylate (2 mg) + Doxazosin mesylate (4 mg)Kit; TabletOralAstrazeneca AbNot applicableNot applicableCanada flag
Cardura-1,2,and 4Doxazosin mesylate (1 mg) + Doxazosin mesylate (2 mg) + Doxazosin mesylate (4 mg)Kit; TabletOralAstrazeneca AbNot applicableNot applicableCanada flag

Categories

ATC Codes
C02CA04 — DoxazosinG04CA55 — Doxazosin and finasteride
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
N-arylpiperazines
Alternative Parents
Quinazolinamines / Benzo-1,4-dioxanes / Anisoles / Dialkylarylamines / Alkyl aryl ethers / Aminopyrimidines and derivatives / Para dioxins / Imidolactams / Tertiary carboxylic acid amides / Heteroaromatic compounds
show 8 more
Substituents
Alkyl aryl ether / Amine / Amino acid or derivatives / Aminopyrimidine / Anisole / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzo-1,4-dioxane / Benzodioxane
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-arylpiperazine, monocarboxylic acid amide, aromatic amine, quinazolines, benzodioxine, N-acylpiperazine (CHEBI:4708)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
NW1291F1W8
CAS number
74191-85-8
InChI Key
RUZYUOTYCVRMRZ-UHFFFAOYSA-N
InChI
InChI=1S/C23H25N5O5/c1-30-18-11-14-15(12-19(18)31-2)25-23(26-21(14)24)28-9-7-27(8-10-28)22(29)20-13-32-16-5-3-4-6-17(16)33-20/h3-6,11-12,20H,7-10,13H2,1-2H3,(H2,24,25,26)
IUPAC Name
2-[4-(2,3-dihydro-1,4-benzodioxine-2-carbonyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine
SMILES
COC1=C(OC)C=C2C(N)=NC(=NC2=C1)N1CCN(CC1)C(=O)C1COC2=CC=CC=C2O1

References

Synthesis Reference

K. S. Keshava Murthy, Gamini Weeratunga, Tianhao Zhou, Bhaskar Reddy Guntoori, "Process for the manufacture of intermediates suitable to make doxazosin, terazosin, prazosin, tiodazosin and related antihypertensive medicines." U.S. Patent US5919931, issued September, 1986.

US5919931
General References
  1. Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT Jr, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM: Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404. [Article]
  2. Rao G: Diagnosis, Epidemiology, and Management of Hypertension in Children. Pediatrics. 2016 Aug;138(2). pii: peds.2015-3616. doi: 10.1542/peds.2015-3616. Epub 2016 Jul 12. [Article]
  3. Liatsikos EN, Katsakiori PF, Assimakopoulos K, Voudoukis T, Kallidonis P, Constantinides C, Athanasopoulos A, Stolzenburg JU, Perimenis P: Doxazosin for the management of distal-ureteral stones. J Endourol. 2007 May;21(5):538-41. doi: 10.1089/end.2006.0107. [Article]
  4. Kaye B, Cussans NJ, Faulkner JK, Stopher DA, Reid JL: The metabolism and kinetics of doxazosin in man, mouse, rat and dog. Br J Clin Pharmacol. 1986;21 Suppl 1:19S-25S. doi: 10.1111/j.1365-2125.1986.tb02849.x. [Article]
  5. Young RA, Brogden RN: Doxazosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in mild or moderate hypertension. Drugs. 1988 May;35(5):525-41. doi: 10.2165/00003495-198835050-00003. [Article]
  6. Doggrell SA: After ALLHAT: doxazosin for the treatment of benign prostatic hyperplasia. Expert Opin Pharmacother. 2004 Sep;5(9):1957-64. doi: 10.1517/14656566.5.9.1957 . [Article]
  7. Elliott HL, Meredith PA, Reid JL: Pharmacokinetic overview of doxazosin. Am J Cardiol. 1987 May 29;59(14):78G-81G. doi: 10.1016/0002-9149(87)90162-7. [Article]
  8. Kaplan SA: alpha-Blocker Therapy: Current Update. Rev Urol. 2005;7 Suppl 8:S34-42. [Article]
  9. Pahuja A, Bashir J, Williamson EM, Barber N: Unresolved priapism secondary to tamsulosin. Int J Impot Res. 2005 May-Jun;17(3):293-4. doi: 10.1038/sj.ijir.3901281. [Article]
  10. Satar S, Sebe A, Avci A, Yesilagac H, Gokel Y: Acute intoxication with doxazosin. Hum Exp Toxicol. 2005 Jun;24(6):337-9. doi: 10.1191/0960327105ht531oa. [Article]
  11. Cubeddu LX, Fuenmayor N, Caplan N, Ferry D: Clinical pharmacology of doxazosin in patients with essential hypertension. Clin Pharmacol Ther. 1987 Apr;41(4):439-49. doi: 10.1038/clpt.1987.54. [Article]
  12. Schwinn DA, Roehrborn CG: Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008 Mar;15(3):193-9. doi: 10.1111/j.1442-2042.2007.01956.x. [Article]
  13. Martin DJ, Lluel P, Guillot E, Coste A, Jammes D, Angel I: Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1 adrenoceptor antagonists. J Pharmacol Exp Ther. 1997 Jul;282(1):228-35. [Article]
  14. Thomas D, Wimmer AB, Wu K, Hammerling BC, Ficker EK, Kuryshev YA, Kiehn J, Katus HA, Schoels W, Karle CA: Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):462-72. Epub 2004 Apr 20. [Article]
  15. Thomas D, Bloehs R, Koschny R, Ficker E, Sykora J, Kiehn J, Schlomer K, Gierten J, Kathofer S, Zitron E, Scholz EP, Kiesecker C, Katus HA, Karle CA: Doxazosin induces apoptosis of cells expressing hERG K+ channels. Eur J Pharmacol. 2008 Jan 28;579(1-3):98-103. doi: 10.1016/j.ejphar.2007.10.051. Epub 2007 Dec 4. [Article]
  16. Jehle J, Schweizer PA, Katus HA, Thomas D: Novel roles for hERG K(+) channels in cell proliferation and apoptosis. Cell Death Dis. 2011 Aug 18;2:e193. doi: 10.1038/cddis.2011.77. [Article]
  17. Hammond KP, Nielsen C, Linnebur SA, Langness JA, Ray G, Maroni P, Kiser JJ: Priapism induced by boceprevir-CYP3A4 inhibition and alpha-adrenergic blockade: case report. Clin Infect Dis. 2014 Jan;58(1):e35-8. doi: 10.1093/cid/cit673. Epub 2013 Oct 2. [Article]
  18. Ferry DG, Caplan NB, Cubeddu LX: Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein. J Pharm Sci. 1986 Feb;75(2):146-9. doi: 10.1002/jps.2600750208. [Article]
  19. Doxazosin FDA label [Link]
  20. FDA approval package, Cardura [Link]
  21. MSDS, Pfizer [Link]
  22. Cardura XL label [Link]
  23. Cardura monograph [Link]
  24. FDA Approved Drug Products: CARDURA (doxazosin mesylate) tablets [Link]
  25. FDA Approved Drug Products: CARDURA XL (doxazosin) extended release tablets [Link]
Human Metabolome Database
HMDB0014728
KEGG Drug
D07874
KEGG Compound
C06970
PubChem Compound
3157
PubChem Substance
46506825
ChemSpider
3045
BindingDB
86731
RxNav
49276
ChEBI
4708
ChEMBL
CHEMBL707
Therapeutic Targets Database
DAP000381
PharmGKB
PA449407
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Doxazosin

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 AvailableBenign Prostatic Hyperplasia (BPH)1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Hypertension / Myocardial Infarction1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableCoronavirus Disease 2019 (COVID‑19) / COVID / Hypertension1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableProstatic Hyperplasia3somestatusstop reasonjust information to hide
Not AvailableCompletedBasic ScienceBenign Prostatic Hyperplasia (BPH)1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Pfizer inc
  • Pfizer laboratories div pfizer inc
  • Actavis elizabeth llc
  • Apotex inc
  • Dava pharmaceuticals inc
  • Genpharm inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Kv pharmaceutical co
  • Mylan pharmaceuticals inc
  • Pliva inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
Packagers
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Cardinal Health
  • DAVA Pharmaceuticals
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • General Injectables and Vaccines Inc.
  • Golden State Medical Supply Inc.
  • Heartland Repack Services LLC
  • International Laboratories Inc.
  • Ivax Pharmaceuticals
  • Legacy Pharmaceuticals Packaging LLC
  • Major Pharmaceuticals
  • Merrell Pharmaceuticals Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Patheon Inc.
  • Pfizer Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Redpharm Drug
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • US Pharmaceutical Group
  • Vangard Labs Inc.
Dosage Forms
FormRouteStrength
TabletOral1 mg / tab
TabletOral2 mg / tab
TabletOral4 mg / tab
Tablet, extended releaseOral8 MG
TabletOral
TabletOral2.000 mg
TabletOral4.000 mg
Tablet, film coated, extended releaseOral4 mg/1
Tablet, film coated, extended releaseOral8 mg/1
Tablet, multilayer, extended releaseOral4 mg/1
Tablet, multilayer, extended releaseOral8 mg/1
Kit; tabletOral
TabletOral400000 mg
TabletOral8 MG
Tablet, extended releaseOral
TabletOral1 mg/1
TabletOral2 mg/1
TabletOral4 mg/1
TabletOral1.26 MG
TabletOral2.42 MG
TabletOral8 mg/1
Tablet, extended releaseOral4 mg
TabletOral1 mg
TabletOral2 mg
TabletOral4 mg
Prices
Unit descriptionCostUnit
Cardura XL 4 mg 24 Hour tablet2.22USD tablet
Cardura xl 8 mg tablet2.04USD tablet
Cardura xl 4 mg tablet1.94USD tablet
Cardura 8 mg tablet1.93USD tablet
Cardura 4 mg tablet1.89USD tablet
Cardura 2 mg tablet1.81USD tablet
Cardura 1 mg tablet1.72USD tablet
Doxazosin mesylate 8 mg tablet1.04USD tablet
Cardura 4 mg Tablet1.0USD tablet
Doxazosin mesylate 4 mg tablet0.99USD tablet
Doxazosin mesylate 1 mg tablet0.94USD tablet
Doxazosin mesylate 2 mg tablet0.94USD tablet
Cardura 2 mg Tablet0.77USD tablet
Cardura 1 mg Tablet0.64USD tablet
Apo-Doxazosin 4 mg Tablet0.56USD tablet
Mylan-Doxazosin 4 mg Tablet0.56USD tablet
Novo-Doxazosin 4 mg Tablet0.56USD tablet
Pms-Doxazosin 4 mg Tablet0.56USD tablet
Apo-Doxazosin 2 mg Tablet0.43USD tablet
Mylan-Doxazosin 2 mg Tablet0.43USD tablet
Novo-Doxazosin 2 mg Tablet0.43USD tablet
Pms-Doxazosin 2 mg Tablet0.43USD tablet
Apo-Doxazosin 1 mg Tablet0.36USD tablet
Mylan-Doxazosin 1 mg Tablet0.36USD tablet
Novo-Doxazosin 1 mg Tablet0.36USD tablet
Pms-Doxazosin 1 mg Tablet0.36USD tablet
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)275-277https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3285710.htm
boiling point (°C)718https://www.scbt.com/scbt/product/doxazosin-mesylate-77883-43-3
water solubility0.8%https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019668s021lbl.pdf
logP2.1https://pubchem.ncbi.nlm.nih.gov/compound/Doxazosin
pKa6.52https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL707/
Predicted Properties
PropertyValueSource
Water Solubility0.79 mg/mLALOGPS
logP2.53ALOGPS
logP2.14Chemaxon
logS-2.8ALOGPS
pKa (Strongest Acidic)12.67Chemaxon
pKa (Strongest Basic)7.24Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count9Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area112.27 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity121.64 m3·mol-1Chemaxon
Polarizability47.17 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9627
Caco-2 permeable+0.7863
P-glycoprotein substrateSubstrate0.7303
P-glycoprotein inhibitor INon-inhibitor0.7391
P-glycoprotein inhibitor IINon-inhibitor0.9528
Renal organic cation transporterNon-inhibitor0.6909
CYP450 2C9 substrateNon-substrate0.9011
CYP450 2D6 substrateNon-substrate0.8195
CYP450 3A4 substrateSubstrate0.7228
CYP450 1A2 substrateNon-inhibitor0.8293
CYP450 2C9 inhibitorNon-inhibitor0.9161
CYP450 2D6 inhibitorNon-inhibitor0.9533
CYP450 2C19 inhibitorNon-inhibitor0.9084
CYP450 3A4 inhibitorNon-inhibitor0.8002
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9078
Ames testNon AMES toxic0.5648
CarcinogenicityNon-carcinogens0.8905
BiodegradationNot ready biodegradable0.9854
Rat acute toxicity2.1954 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8602
hERG inhibition (predictor II)Inhibitor0.823
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-MSsplash10-000i-0792300000-541be6ba12e92be79321
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0010900000-9601aa919c95799ec009
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0kei-0981100000-a9ee3121ba6832366f8e
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0970000000-5261f1bc60ceee4364de
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0950000000-f649236044e4e2a5de38
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-1920000000-86655cc3bb892d757068
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-1900000000-88bca2ddf2930fa0c468
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0000900000-449254642300c1324285
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0002900000-3097c8a3403b52610918
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0079100000-06d36a9b7afe6cf0c6e9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000t-1091000000-cbd9b2106818ef5fd2ba
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-1190000000-a1c84b0c3657d8000e35
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-1390000000-e802cb93ca8d6934ee96
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-0002900000-738284cd2b649e7cf210
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udl-0009600000-718a4ebd8a14a78e2346
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0zfu-0009500000-6c1440dced500c6aaf34
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0009200000-bb600feebb0c89039dd7
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-05fv-1295100000-d969001ddd24b795d975
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4r-1465900000-257e0e4376fcc1ad5195
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-0002900000-738284cd2b649e7cf210
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udl-0019400000-01ad06865309d5465e0f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0zfu-0009500000-09d683531c0c1f1b84b7
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0009100000-570bce7a1849bde16f82
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-05tg-0295200000-d35c01d476c274acfadc
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0kfw-1496800000-767a1b0562d320204e4e
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]-237.701956
predicted
DarkChem Lite v0.1.0
[M-H]-194.00697
predicted
DeepCCS 1.0 (2019)
[M-H]-237.701956
predicted
DarkChem Lite v0.1.0
[M-H]-237.701956
predicted
DarkChem Lite v0.1.0
[M-H]-194.00697
predicted
DeepCCS 1.0 (2019)
[M-H]-194.00697
predicted
DeepCCS 1.0 (2019)
[M+H]+237.511756
predicted
DarkChem Lite v0.1.0
[M+H]+196.36497
predicted
DeepCCS 1.0 (2019)
[M+H]+237.511756
predicted
DarkChem Lite v0.1.0
[M+H]+237.511756
predicted
DarkChem Lite v0.1.0
[M+H]+196.36497
predicted
DeepCCS 1.0 (2019)
[M+H]+196.36497
predicted
DeepCCS 1.0 (2019)
[M+Na]+236.956256
predicted
DarkChem Lite v0.1.0
[M+Na]+202.68077
predicted
DeepCCS 1.0 (2019)
[M+Na]+236.956256
predicted
DarkChem Lite v0.1.0
[M+Na]+236.956256
predicted
DarkChem Lite v0.1.0
[M+Na]+202.68077
predicted
DeepCCS 1.0 (2019)
[M+Na]+202.68077
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
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. Yono M, Foster HE Jr, Shin D, Takahashi W, Pouresmail M, Latifpour J: Doxazosin-induced up-regulation of alpha 1A-adrenoceptor mRNA in the rat lower urinary tract. Can J Physiol Pharmacol. 2004 Oct;82(10):872-8. [Article]
  2. Michel MC, Grubbel B, Taguchi K, Verfurth F, Otto T, Kropfl D: Drugs for treatment of benign prostatic hyperplasia: affinity comparison at cloned alpha 1-adrenoceptor subtypes and in human prostate. J Auton Pharmacol. 1996 Feb;16(1):21-8. [Article]
  3. Roehrborn CG, Schwinn DA: Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol. 2004 Mar;171(3):1029-35. [Article]
  4. Ishizuka O, Pandita RK, Mattiasson A, Steers WD, Andersson KE: Stimulation of bladder activity by volume, L-dopa and capsaicin in normal conscious rats--effects of spinal alpha 1-adrenoceptor blockade. Naunyn Schmiedebergs Arch Pharmacol. 1997 Jun;355(6):787-93. [Article]
  5. Bae JH, Jung PB, Lee JG: The effects of alpha-adrenoceptor antagonists on the urethral perfusion pressure of the female rat. BJU Int. 2005 Nov;96(7):1131-5. [Article]
  6. Greco KA, McVary KT: The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43. doi: 10.1038/ijir.2008.51. [Article]
  7. Shannon R, Chaudhry M: Effect of alpha1-adrenergic receptors in cardiac pathophysiology. Am Heart J. 2006 Nov;152(5):842-50. [Article]
  8. Martin DJ: Preclinical pharmacology of alpha1-adrenoceptor antagonists. Eur Urol. 1999;36 Suppl 1:35-41; discussion 65. [Article]
  9. Schwinn DA, Roehrborn CG: Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008 Mar;15(3):193-9. doi: 10.1111/j.1442-2042.2007.01956.x. [Article]
  10. Martin DJ, Lluel P, Guillot E, Coste A, Jammes D, Angel I: Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1 adrenoceptor antagonists. J Pharmacol Exp Ther. 1997 Jul;282(1):228-35. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
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. Martin DJ, Lluel P, Guillot E, Coste A, Jammes D, Angel I: Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1 adrenoceptor antagonists. J Pharmacol Exp Ther. 1997 Jul;282(1):228-35. [Article]
  2. Schwinn DA, Roehrborn CG: Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008 Mar;15(3):193-9. doi: 10.1111/j.1442-2042.2007.01956.x. [Article]
  3. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
This is a potential target action of doxazosin that was demonstrated by in vitro studies.
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

Components:
References
  1. Thomas D, Wimmer AB, Wu K, Hammerling BC, Ficker EK, Kuryshev YA, Kiehn J, Katus HA, Schoels W, Karle CA: Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):462-72. Epub 2004 Apr 20. [Article]
  2. Thomas D, Bloehs R, Koschny R, Ficker E, Sykora J, Kiehn J, Schlomer K, Gierten J, Kathofer S, Zitron E, Scholz EP, Kiesecker C, Katus HA, Karle CA: Doxazosin induces apoptosis of cells expressing hERG K+ channels. Eur J Pharmacol. 2008 Jan 28;579(1-3):98-103. doi: 10.1016/j.ejphar.2007.10.051. Epub 2007 Dec 4. [Article]
  3. Jehle J, Schweizer PA, Katus HA, Thomas D: Novel roles for hERG K(+) channels in cell proliferation and apoptosis. Cell Death Dis. 2011 Aug 18;2:e193. doi: 10.1038/cddis.2011.77. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Schwinn DA, Roehrborn CG: Alpha1-adrenoceptor subtypes and lower urinary tract symptoms. Int J Urol. 2008 Mar;15(3):193-9. doi: 10.1111/j.1442-2042.2007.01956.x. [Article]
  2. Martin DJ, Lluel P, Guillot E, Coste A, Jammes D, Angel I: Comparative alpha-1 adrenoceptor subtype selectivity and functional uroselectivity of alpha-1 adrenoceptor antagonists. J Pharmacol Exp Ther. 1997 Jul;282(1):228-35. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. Hammond KP, Nielsen C, Linnebur SA, Langness JA, Ray G, Maroni P, Kiser JJ: Priapism induced by boceprevir-CYP3A4 inhibition and alpha-adrenergic blockade: case report. Clin Infect Dis. 2014 Jan;58(1):e35-8. doi: 10.1093/cid/cit673. Epub 2013 Oct 2. [Article]
  2. Dailymed [Link]
  3. Cardura XL label [Link]
  4. Cardura monograph [Link]
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. Hammond KP, Nielsen C, Linnebur SA, Langness JA, Ray G, Maroni P, Kiser JJ: Priapism induced by boceprevir-CYP3A4 inhibition and alpha-adrenergic blockade: case report. Clin Infect Dis. 2014 Jan;58(1):e35-8. doi: 10.1093/cid/cit673. Epub 2013 Oct 2. [Article]
  2. Cardura XL 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 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. Cardura monograph [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Hammond KP, Nielsen C, Linnebur SA, Langness JA, Ray G, Maroni P, Kiser JJ: Priapism induced by boceprevir-CYP3A4 inhibition and alpha-adrenergic blockade: case report. Clin Infect Dis. 2014 Jan;58(1):e35-8. doi: 10.1093/cid/cit673. Epub 2013 Oct 2. [Article]
  2. Cardura XL label [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
This transporter action is supported by in vitro data only.
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. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K: Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500. [Article]
  2. Takara K, Sakaeda T, Kakumoto M, Tanigawara Y, Kobayashi H, Okumura K, Ohnishi N, Yokoyama T: Effects of alpha-adrenoceptor antagonist doxazosin on MDR1-mediated multidrug resistance and transcellular transport. Oncol Res. 2009;17(11-12):527-33. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
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. Stage TB, Brosen K, Christensen MM: A Comprehensive Review of Drug-Drug Interactions with Metformin. Clin Pharmacokinet. 2015 Aug;54(8):811-24. doi: 10.1007/s40262-015-0270-6. [Article]
  2. Dujic T, Zhou K, Donnelly LA, Tavendale R, Palmer CN, Pearson ER: Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study. Diabetes. 2015 May;64(5):1786-93. doi: 10.2337/db14-1388. Epub 2014 Dec 15. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 21, 2024 12:36