Identification

Name
Doxazosin
Accession Number
DB00590  (APRD00474)
Type
Small Molecule
Groups
Approved
Description

Doxazosin is a quinazoline-derivative that selectively antagonizes postsynaptic α1-adrenergic receptors. It may be used to mild to moderate hypertension and in the management of symptomatic benign prostatic hyperplasia (BPH). α1-Receptors mediate contraction and hypertrophic growth of smooth muscle cells. Antagonism of these receptors leads to smooth muscle relaxation in the peripheral vasculature and prostate gland.

Structure
Thumb
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
  • Doxazosina
  • Doxazosine
  • Doxazosinum
Product Ingredients
IngredientUNIICASInChI Key
Doxazosin mesylate86P6PQK0MU77883-43-3VJECBOKJABCYMF-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CarduraTablet8 mg/1OralRoerig1990-11-02Not applicableUs
CarduraTablet2 mg/1OralRoerig1990-11-02Not applicableUs
CarduraTablet4 mg/1OralPhysicians Total Care, Inc.1993-06-222012-07-16Us
CarduraTablet1 mg/1OralRoerig1990-11-02Not applicableUs
CarduraTablet2 mg/1OralPhysicians Total Care, Inc.1999-02-102012-06-30Us
CarduraTablet4 mg/1OralRoerig1990-11-02Not applicableUs
CarduraTablet8 mg/1OralPhysicians Total Care, Inc.1994-12-132012-06-30Us
CarduraTablet1 mg/1OralPhysicians Total Care, Inc.1995-10-162012-06-30Us
Cardura XLTablet, multilayer, extended release4 mg/1OralRoerig2005-02-22Not applicableUs
Cardura XLTablet, multilayer, extended release8 mg/1OralRoerig2005-02-22Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-doxazosinTablet1 mgOralApotex Corporation1999-07-22Not applicableCanada
Apo-doxazosinTablet4 mgOralApotex Corporation1999-07-22Not applicableCanada
Apo-doxazosinTablet2 mgOralApotex Corporation1999-07-22Not applicableCanada
Dom-doxazosinTablet2 mgOralDominion Pharmacal2004-05-26Not applicableCanada
Dom-doxazosinTablet1 mgOralDominion Pharmacal2004-05-26Not applicableCanada
Dom-doxazosinTablet4 mgOralDominion Pharmacal2004-05-26Not applicableCanada
DoxazosinTablet4 mg/1OralUnit Dose Services2014-09-09Not applicableUs50436 631220180913 8702 g05yt1
DoxazosinTablet4 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs2000-10-19Not applicableUs
DoxazosinTablet2 mg/1OralPd Rx Pharmaceuticals, Inc.2000-10-20Not applicableUs
DoxazosinTablet1 mg/1OralNucare Pharmaceuticals,inc.2015-03-04Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Cardura-1,2,and 4Doxazosin (1 mg) + Doxazosin (2 mg) + Doxazosin (4 mg)Kit; TabletOralAstra ZenecaNot applicableNot applicableCanada
Cardura-1,2,and 4Doxazosin (1 mg) + Doxazosin (2 mg) + Doxazosin (4 mg)Kit; TabletOralAstra ZenecaNot applicableNot applicableCanada
Cardura-1,2,and 4Doxazosin (1 mg) + Doxazosin (2 mg) + Doxazosin (4 mg)Kit; TabletOralAstra ZenecaNot applicableNot applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Doxazosin mesylateDoxazosin mesylate (8 mg/1)TabletOralKV Pharmaceuticals2006-12-15Not applicableUs
Doxazosin mesylateDoxazosin mesylate (1 mg/1)TabletOralKV Pharmaceuticals2006-12-15Not applicableUs
Doxazosin mesylateDoxazosin mesylate (4 mg/1)TabletOralKV Pharmaceuticals2006-12-15Not applicableUs
Doxazosin mesylateDoxazosin mesylate (2 mg/1)TabletOralKV Pharmaceuticals2006-12-15Not applicableUs
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))
Categories
UNII
NW1291F1W8
CAS number
74191-85-8
Weight
Average: 451.4751
Monoisotopic: 451.185568935
Chemical Formula
C23H25N5O5
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

Pharmacology

Indication

For treatment and management of mild to moderate hypertension and urinary obstruction symptoms caused by BPH.

Associated Conditions
Pharmacodynamics

Doxazosin is an alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Accordingly, Doxazosin is a selective inhibitor of the alpha1 subtype of alpha adrenergic receptors. In the human prostate, Doxazosin antagonizes phenylephrine (alpha1 agonist)-induced contractions, in vitro, and binds with high affinity to the alpha1a adrenoceptor, which is thought to be the predominant functional type in the prostate. Studies in normal human subjects have shown that Doxazosin competitively antagonized the pressor effects of phenylephrine (an alpha1 agonist) and the systolic pressor effect of norepinephrine. The antihypertensive effect of Doxazosin results from a decrease in systemic vascular resistance and the parent compound Doxazosin is primarily responsible for the antihypertensive activity.

Mechanism of action

Doxazosin acts by inhibiting the postsynaptic alpha(1)-adrenoceptors on vascular smooth muscle. This inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation.

TargetActionsOrganism
AAlpha-1A adrenergic receptor
antagonist
Human
AAlpha-1B adrenergic receptor
antagonist
Human
AAlpha-1D adrenergic receptor
antagonist
Human
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Human
UPotassium voltage-gated channel subfamily H member 6
inhibitor
Human
UPotassium voltage-gated channel subfamily H member 7
inhibitor
Human
Absorption

65%

Volume of distribution
Not Available
Protein binding

98%

Metabolism

Hepatic.

Route of elimination

On average only 4.8% of the dose was excreted as unchanged drug in the feces and only a trace of the total radioactivity in the urine was attributed to unchanged drug.

Half life

22 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include hypotension. Oral LD50 is greater than 1000 mg/kg in mice and rats.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Doxazosin.
AbediterolThe therapeutic efficacy of Abediterol can be decreased when used in combination with Doxazosin.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Doxazosin.
AcebutololAcebutolol may increase the orthostatic hypotensive activities of Doxazosin.
AceclofenacThe therapeutic efficacy of Doxazosin can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Doxazosin can be decreased when used in combination with Acemetacin.
AcepromazineDoxazosin may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Acepromazine.
Acetylsalicylic acidThe therapeutic efficacy of Doxazosin can be decreased when used in combination with Acetylsalicylic acid.
AdrafinilThe therapeutic efficacy of Adrafinil can be decreased when used in combination with Doxazosin.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Doxazosin.
Food Interactions
  • Avoid alcohol.
  • Avoid natural licorice.
  • Take without regard to meals.

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. [PubMed:12461301]
External Links
Human Metabolome Database
HMDB0014728
KEGG Drug
D07874
KEGG Compound
C06970
PubChem Compound
3157
PubChem Substance
46506825
ChemSpider
3045
BindingDB
86731
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
ATC Codes
C02CA04 — Doxazosin
AHFS Codes
  • 24:20.00 — Alpha-adrenergic Blocking Agents
FDA label
Download (511 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableCocaine Abuse / Dependence, Cocaine / Substance Abuse1
1CompletedNot AvailableSubstance-Related Disorders1
1CompletedBasic ScienceAmphetamine-Related Disorders / Moods Disorders / Substance-Related Disorders1
1CompletedTreatmentDependence, Cocaine1
1CompletedTreatmentErectile Dysfunction (ED)1
1CompletedTreatmentHealthy Volunteers1
1Not Yet RecruitingOtherAlcohol Use Disorder (AUD)1
1RecruitingTreatmentDependence, Cocaine1
1RecruitingTreatmentPTSD1
1, 2CompletedTreatmentMethamphetamine or Cocaine Dependence1
1, 2RecruitingTreatmentAlcohol Use Disorder (AUD) / PTSD1
2CompletedDiagnosticDependence, Cocaine1
2CompletedTreatmentAlcohol Dependence / Feeling Anxious1
2CompletedTreatmentBenign Prostatic Hyperplasia (BPH)1
2CompletedTreatmentCardiovascular Disease (CVD) / Heart Diseases / High Blood Pressure (Hypertension) / Vascular Diseases1
2CompletedTreatmentDependence, Cocaine1
2CompletedTreatmentSmoking1
2RecruitingTreatmentAlcohol Use Disorders (AUD) / Posttraumatic Stress Disorders / PTSD1
2RecruitingTreatmentAlcoholism1
2RecruitingTreatmentStress Disorders, Post-Traumatic1
2, 3RecruitingTreatmentHigh Blood Pressure (Hypertension)1
3CompletedPreventionCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / Heart Diseases / Heart Failure, Unspecified / High Blood Cholesterol Level / High Blood Pressure (Hypertension) / Myocardial Infarction / Myocardial Ischemia1
3CompletedTreatmentProstatic Hyperplasia / Prostatic Hypertrophy, Benign1
3RecruitingTreatmentChronic Kidney Disease Requiring Chronic Dialysis / Hyperphosphataemia1
3RecruitingTreatmentParaganglioma / Pheochromocytomas1
3Unknown StatusTreatmentRenal Stones1
4Active Not RecruitingTreatmentHypertension, Resistant to Conventional Therapy1
4CompletedBasic ScienceIdiopathic Dilated Cardiomyopathy1
4CompletedTreatmentCardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Hypertension,Essential / Strokes1
4CompletedTreatmentHigh Blood Pressure (Hypertension)5
4CompletedTreatmentPheochromocytomas1
4CompletedTreatmentStress Disorders, Post-Traumatic1
4Unknown StatusPreventionDiabetic Nephropathies1
4WithdrawnTreatmentBenign Prostatic Hyperplasia (BPH)1
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / High Blood Pressure (Hypertension) / Myocardial Infarction1
Not AvailableCompletedBasic ScienceBenign Prostatic Hyperplasia (BPH)1
Not AvailableTerminatedTreatmentHigh Blood Pressure (Hypertension) / Microvascular Angina1
Not AvailableTerminatedTreatmentProstatic Hyperplasia / Urinary Retention1

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
Tablet, multilayer, extended releaseOral4 mg/1
Tablet, multilayer, extended releaseOral8 mg/1
TabletOral1 mg
Kit; tabletOral
TabletOral2 mg
TabletOral4 mg
TabletOral1 mg/1
TabletOral2 mg/1
TabletOral4 mg/1
TabletOral8 mg/1
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)289-290 °CNot Available
water solubility24 mg/LNot Available
logP2.1Not Available
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
Polarizability46.63 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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
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

Taxonomy

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
N-arylpiperazine / Quinazolinamine / Diazanaphthalene / Benzo-1,4-dioxane / Benzodioxane / Quinazoline / Anisole / Dialkylarylamine / Alkyl aryl ether / Aminopyrimidine
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-arylpiperazine, monocarboxylic acid amide, aromatic amine, quinazolines, benzodioxine, N-acylpiperazine (CHEBI:4708)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific 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) prot...
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. [PubMed:15573147]
  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. [PubMed:8736427]
  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. [PubMed:14767264]
  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. [PubMed:9205965]
  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. [PubMed:16225542]
  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. [PubMed:19002123]
  7. Shannon R, Chaudhry M: Effect of alpha1-adrenergic receptors in cardiac pathophysiology. Am Heart J. 2006 Nov;152(5):842-50. [PubMed:17070143]
  8. Martin DJ: Preclinical pharmacology of alpha1-adrenoceptor antagonists. Eur Urol. 1999;36 Suppl 1:35-41; discussion 65. [PubMed:10393471]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific 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) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Lepor H: Alpha blockers for the treatment of benign prostatic hyperplasia. Rev Urol. 2007 Fall;9(4):181-90. [PubMed:18231614]
  2. 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. [PubMed:19002123]
  3. Shannon R, Chaudhry M: Effect of alpha1-adrenergic receptors in cardiac pathophysiology. Am Heart J. 2006 Nov;152(5):842-50. [PubMed:17070143]
  4. Martin DJ: Preclinical pharmacology of alpha1-adrenoceptor antagonists. Eur Urol. 1999;36 Suppl 1:35-41; discussion 65. [PubMed:10393471]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Lepor H: Alpha blockers for the treatment of benign prostatic hyperplasia. Rev Urol. 2007 Fall;9(4):181-90. [PubMed:18231614]
  2. 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. [PubMed:19002123]
  3. Shannon R, Chaudhry M: Effect of alpha1-adrenergic receptors in cardiac pathophysiology. Am Heart J. 2006 Nov;152(5):842-50. [PubMed:17070143]
  4. Martin DJ: Preclinical pharmacology of alpha1-adrenoceptor antagonists. Eur Urol. 1999;36 Suppl 1:35-41; discussion 65. [PubMed:10393471]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
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. [PubMed:15098086]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity
Specific Function
Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current (By similarity). Channel properties may be modulated by cAMP and subunit assembly.
Gene Name
KCNH6
Uniprot ID
Q9H252
Uniprot Name
Potassium voltage-gated channel subfamily H member 6
Molecular Weight
109923.705 Da
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. [PubMed:15098086]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity
Specific Function
Pore-forming (alpha) subunit of voltage-gated potassium channel. Channel properties may be modulated by cAMP and subunit assembly.
Gene Name
KCNH7
Uniprot ID
Q9NS40
Uniprot Name
Potassium voltage-gated channel subfamily H member 7
Molecular Weight
134998.525 Da
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. [PubMed:15098086]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
General Function
Not Available
Specific Function
Functions as 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...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. 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. [PubMed:2870173]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
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. [PubMed:11895100]
  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. [PubMed:19806783]

Drug created on June 13, 2005 07:24 / Updated on September 22, 2018 22:24