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Properties

Spectra

Taxonomy

Doxazosin

Targets (6)Enzymes (2)Carriers (1)Transporters (1)Biointeractions (9)

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

Similar Structures

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

Ingredient	UNII	CAS	InChI Key
Doxazosin mesylate	86P6PQK0MU	77883-43-3	VJECBOKJABCYMF-UHFFFAOYSA-N

Product Images

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Cardura	Tablet	8 mg/1	Oral	Roerig	1990-11-02	Not applicable
Cardura	Tablet	2 mg/1	Oral	Roerig	1990-11-02	Not applicable
Cardura	Tablet	4 mg/1	Oral	Physicians Total Care, Inc.	1993-06-22	2012-07-16
Cardura	Tablet	1 mg/1	Oral	Roerig	1990-11-02	Not applicable
Cardura	Tablet	2 mg/1	Oral	Physicians Total Care, Inc.	1999-02-10	2012-06-30
Cardura	Tablet	4 mg/1	Oral	Roerig	1990-11-02	Not applicable
Cardura	Tablet	8 mg/1	Oral	Physicians Total Care, Inc.	1994-12-13	2012-06-30
Cardura	Tablet	1 mg/1	Oral	Physicians Total Care, Inc.	1995-10-16	2012-06-30
Cardura XL	Tablet, multilayer, extended release	4 mg/1	Oral	Roerig	2005-02-22	Not applicable
Cardura XL	Tablet, multilayer, extended release	8 mg/1	Oral	Roerig	2005-02-22	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Apo-doxazosin	Tablet	1 mg	Oral	Apotex Corporation	1999-07-22	Not applicable
Apo-doxazosin	Tablet	4 mg	Oral	Apotex Corporation	1999-07-22	Not applicable
Apo-doxazosin	Tablet	2 mg	Oral	Apotex Corporation	1999-07-22	Not applicable
Dom-doxazosin	Tablet	2 mg	Oral	Dominion Pharmacal	2004-05-26	Not applicable
Dom-doxazosin	Tablet	1 mg	Oral	Dominion Pharmacal	2004-05-26	Not applicable
Dom-doxazosin	Tablet	4 mg	Oral	Dominion Pharmacal	2004-05-26	Not applicable
Doxazosin	Tablet	4 mg/1	Oral	Unit Dose Services	2014-09-09	Not applicable
Doxazosin	Tablet	4 mg/1	Oral	Ncs Health Care Of Ky, Inc Dba Vangard Labs	2000-10-19	Not applicable
Doxazosin	Tablet	2 mg/1	Oral	Pd Rx Pharmaceuticals, Inc.	2000-10-20	Not applicable
Doxazosin	Tablet	1 mg/1	Oral	Nucare Pharmaceuticals,inc.	2015-03-04	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Cardura-1,2,and 4	Doxazosin (1 mg) + Doxazosin (2 mg) + Doxazosin (4 mg)	Kit; Tablet	Oral	Astra Zeneca	Not applicable	Not applicable
Cardura-1,2,and 4	Doxazosin (1 mg) + Doxazosin (2 mg) + Doxazosin (4 mg)	Kit; Tablet	Oral	Astra Zeneca	Not applicable	Not applicable
Cardura-1,2,and 4	Doxazosin (1 mg) + Doxazosin (2 mg) + Doxazosin (4 mg)	Kit; Tablet	Oral	Astra Zeneca	Not applicable	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Doxazosin mesylate	Doxazosin mesylate (8 mg/1)	Tablet	Oral	KV Pharmaceuticals	2006-12-15	Not applicable
Doxazosin mesylate	Doxazosin mesylate (1 mg/1)	Tablet	Oral	KV Pharmaceuticals	2006-12-15	Not applicable
Doxazosin mesylate	Doxazosin mesylate (4 mg/1)	Tablet	Oral	KV Pharmaceuticals	2006-12-15	Not applicable
Doxazosin mesylate	Doxazosin mesylate (2 mg/1)	Tablet	Oral	KV Pharmaceuticals	2006-12-15	Not applicable

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.

Target	Actions	Organism
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

Drug	Interaction
4-Methoxyamphetamine	The therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Doxazosin.
Abediterol	The therapeutic efficacy of Abediterol can be decreased when used in combination with Doxazosin.
Abemaciclib	The serum concentration of Abemaciclib can be increased when it is combined with Doxazosin.
Acebutolol	Acebutolol may increase the orthostatic hypotensive activities of Doxazosin.
Aceclofenac	The therapeutic efficacy of Doxazosin can be decreased when used in combination with Aceclofenac.
Acemetacin	The therapeutic efficacy of Doxazosin can be decreased when used in combination with Acemetacin.
Acepromazine	Doxazosin may increase the orthostatic hypotensive, hypotensive, and antihypertensive activities of Acepromazine.
Acetylsalicylic acid	The therapeutic efficacy of Doxazosin can be decreased when used in combination with Acetylsalicylic acid.
Adrafinil	The therapeutic efficacy of Adrafinil can be decreased when used in combination with Doxazosin.
Afatinib	The 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

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

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Cocaine Abuse / Dependence, Cocaine / Substance Abuse	1
1	Completed	Not Available	Substance-Related Disorders	1
1	Completed	Basic Science	Amphetamine-Related Disorders / Moods Disorders / Substance-Related Disorders	1
1	Completed	Treatment	Dependence, Cocaine	1
1	Completed	Treatment	Erectile Dysfunction (ED)	1
1	Completed	Treatment	Healthy Volunteers	1
1	Not Yet Recruiting	Other	Alcohol Use Disorder (AUD)	1
1	Recruiting	Treatment	Dependence, Cocaine	1
1	Recruiting	Treatment	PTSD	1
1, 2	Completed	Treatment	Methamphetamine or Cocaine Dependence	1
1, 2	Recruiting	Treatment	Alcohol Use Disorder (AUD) / PTSD	1
2	Completed	Diagnostic	Dependence, Cocaine	1
2	Completed	Treatment	Alcohol Dependence / Feeling Anxious	1
2	Completed	Treatment	Benign Prostatic Hyperplasia (BPH)	1
2	Completed	Treatment	Cardiovascular Disease (CVD) / Heart Diseases / High Blood Pressure (Hypertension) / Vascular Diseases	1
2	Completed	Treatment	Dependence, Cocaine	1
2	Completed	Treatment	Smoking	1
2	Recruiting	Treatment	Alcohol Use Disorders (AUD) / Posttraumatic Stress Disorders / PTSD	1
2	Recruiting	Treatment	Alcoholism	1
2	Recruiting	Treatment	Stress Disorders, Post-Traumatic	1
2, 3	Recruiting	Treatment	High Blood Pressure (Hypertension)	1
3	Completed	Prevention	Cardiovascular 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 Ischemia	1
3	Completed	Treatment	Prostatic Hyperplasia / Prostatic Hypertrophy, Benign	1
3	Recruiting	Treatment	Chronic Kidney Disease Requiring Chronic Dialysis / Hyperphosphataemia	1
3	Recruiting	Treatment	Paraganglioma / Pheochromocytomas	1
3	Unknown Status	Treatment	Renal Stones	1
4	Active Not Recruiting	Treatment	Hypertension, Resistant to Conventional Therapy	1
4	Completed	Basic Science	Idiopathic Dilated Cardiomyopathy	1
4	Completed	Treatment	Cardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Hypertension,Essential / Strokes	1
4	Completed	Treatment	High Blood Pressure (Hypertension)	5
4	Completed	Treatment	Pheochromocytomas	1
4	Completed	Treatment	Stress Disorders, Post-Traumatic	1
4	Unknown Status	Prevention	Diabetic Nephropathies	1
4	Withdrawn	Treatment	Benign Prostatic Hyperplasia (BPH)	1
Not Available	Completed	Not Available	Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / High Blood Pressure (Hypertension) / Myocardial Infarction	1
Not Available	Completed	Basic Science	Benign Prostatic Hyperplasia (BPH)	1
Not Available	Terminated	Treatment	High Blood Pressure (Hypertension) / Microvascular Angina	1
Not Available	Terminated	Treatment	Prostatic Hyperplasia / Urinary Retention	1

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

Form	Route	Strength
Tablet, multilayer, extended release	Oral	4 mg/1
Tablet, multilayer, extended release	Oral	8 mg/1
Tablet	Oral	1 mg
Kit; tablet	Oral
Tablet	Oral	2 mg
Tablet	Oral	4 mg
Tablet	Oral	1 mg/1
Tablet	Oral	2 mg/1
Tablet	Oral	4 mg/1
Tablet	Oral	8 mg/1

Prices

Unit description	Cost	Unit
Cardura XL 4 mg 24 Hour tablet	2.22USD	tablet
Cardura xl 8 mg tablet	2.04USD	tablet
Cardura xl 4 mg tablet	1.94USD	tablet
Cardura 8 mg tablet	1.93USD	tablet
Cardura 4 mg tablet	1.89USD	tablet
Cardura 2 mg tablet	1.81USD	tablet
Cardura 1 mg tablet	1.72USD	tablet
Doxazosin mesylate 8 mg tablet	1.04USD	tablet
Cardura 4 mg Tablet	1.0USD	tablet
Doxazosin mesylate 4 mg tablet	0.99USD	tablet
Doxazosin mesylate 1 mg tablet	0.94USD	tablet
Doxazosin mesylate 2 mg tablet	0.94USD	tablet
Cardura 2 mg Tablet	0.77USD	tablet
Cardura 1 mg Tablet	0.64USD	tablet
Apo-Doxazosin 4 mg Tablet	0.56USD	tablet
Mylan-Doxazosin 4 mg Tablet	0.56USD	tablet
Novo-Doxazosin 4 mg Tablet	0.56USD	tablet
Pms-Doxazosin 4 mg Tablet	0.56USD	tablet
Apo-Doxazosin 2 mg Tablet	0.43USD	tablet
Mylan-Doxazosin 2 mg Tablet	0.43USD	tablet
Novo-Doxazosin 2 mg Tablet	0.43USD	tablet
Pms-Doxazosin 2 mg Tablet	0.43USD	tablet
Apo-Doxazosin 1 mg Tablet	0.36USD	tablet
Mylan-Doxazosin 1 mg Tablet	0.36USD	tablet
Novo-Doxazosin 1 mg Tablet	0.36USD	tablet
Pms-Doxazosin 1 mg Tablet	0.36USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	289-290 °C	Not Available
water solubility	24 mg/L	Not Available
logP	2.1	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.79 mg/mL	ALOGPS
logP	2.53	ALOGPS
logP	2.14	ChemAxon
logS	-2.8	ALOGPS
pKa (Strongest Acidic)	12.67	ChemAxon
pKa (Strongest Basic)	7.24	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	9	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	112.27 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	121.64 m³·mol^-1	ChemAxon
Polarizability	46.63 Å³	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9627
Caco-2 permeable	+	0.7863
P-glycoprotein substrate	Substrate	0.7303
P-glycoprotein inhibitor I	Non-inhibitor	0.7391
P-glycoprotein inhibitor II	Non-inhibitor	0.9528
Renal organic cation transporter	Non-inhibitor	0.6909
CYP450 2C9 substrate	Non-substrate	0.9011
CYP450 2D6 substrate	Non-substrate	0.8195
CYP450 3A4 substrate	Substrate	0.7228
CYP450 1A2 substrate	Non-inhibitor	0.8293
CYP450 2C9 inhibitor	Non-inhibitor	0.9161
CYP450 2D6 inhibitor	Non-inhibitor	0.9533
CYP450 2C19 inhibitor	Non-inhibitor	0.9084
CYP450 3A4 inhibitor	Non-inhibitor	0.8002
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9078
Ames test	Non AMES toxic	0.5648
Carcinogenicity	Non-carcinogens	0.8905
Biodegradation	Not ready biodegradable	0.9854
Rat acute toxicity	2.1954 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.8602
hERG inhibition (predictor II)	Inhibitor	0.823

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-0udi-0010900000-9601aa919c95799ec009
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-0kei-0981100000-a9ee3121ba6832366f8e
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-0a4i-0970000000-5261f1bc60ceee4364de
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-0a4i-0950000000-f649236044e4e2a5de38
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-0a4i-1920000000-86655cc3bb892d757068
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-0a4i-1900000000-88bca2ddf2930fa0c468
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0udi-0000900000-449254642300c1324285
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0udi-0002900000-3097c8a3403b52610918
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0006-0079100000-06d36a9b7afe6cf0c6e9
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-000t-1091000000-cbd9b2106818ef5fd2ba
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-001i-1190000000-a1c84b0c3657d8000e35
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-001i-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

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	0.537	N/A	N/A	19719240
Ki (nM)	2.6	N/A	N/A	7658428

Details1. Alpha-1A adrenergic receptor

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

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]
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]
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]
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]
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]
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]
Shannon R, Chaudhry M: Effect of alpha1-adrenergic receptors in cardiac pathophysiology. Am Heart J. 2006 Nov;152(5):842-50. [PubMed:17070143]
Martin DJ: Preclinical pharmacology of alpha1-adrenoceptor antagonists. Eur Urol. 1999;36 Suppl 1:35-41; discussion 65. [PubMed:10393471]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	0.74	N/A	N/A	7658428
Ki (nM)	0.813	N/A	N/A	19719240

Details2. Alpha-1B adrenergic receptor

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

Lepor H: Alpha blockers for the treatment of benign prostatic hyperplasia. Rev Urol. 2007 Fall;9(4):181-90. [PubMed:18231614]
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]
Shannon R, Chaudhry M: Effect of alpha1-adrenergic receptors in cardiac pathophysiology. Am Heart J. 2006 Nov;152(5):842-50. [PubMed:17070143]
Martin DJ: Preclinical pharmacology of alpha1-adrenoceptor antagonists. Eur Urol. 1999;36 Suppl 1:35-41; discussion 65. [PubMed:10393471]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	0.813	N/A	N/A	19719240
Ki (nM)	1.2	N/A	N/A	7658428

Details3. Alpha-1D adrenergic receptor

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

Lepor H: Alpha blockers for the treatment of benign prostatic hyperplasia. Rev Urol. 2007 Fall;9(4):181-90. [PubMed:18231614]
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]
Shannon R, Chaudhry M: Effect of alpha1-adrenergic receptors in cardiac pathophysiology. Am Heart J. 2006 Nov;152(5):842-50. [PubMed:17070143]
Martin DJ: Preclinical pharmacology of alpha1-adrenoceptor antagonists. Eur Urol. 1999;36 Suppl 1:35-41; discussion 65. [PubMed:10393471]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	588.84	N/A	N/A	21185626

Details4. Potassium voltage-gated channel subfamily H member 2

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

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]

Details5. Potassium voltage-gated channel subfamily H member 6

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

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]

Details6. Potassium voltage-gated channel subfamily H member 7

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

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

Details1. Cytochrome P450 2C19

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

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]

Details2. Cytochrome P450 2D6

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

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

Details1. Alpha-1-acid glycoprotein 1

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

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

Details1. Multidrug resistance protein 1

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

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]
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

Doxazosin

Identification

Structure for Doxazosin (DB00590)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

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Enzymes

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Carriers

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Transporters

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