Drug/Small Molecule:

doxazosin

Overview

IUPAC Name:	[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(2,3-dihydro-1,4-benzodioxin-2-yl)methanone
Trade Names:	Alfadil; Cardenalin; Cardular; Cardura; Cardura-1; Cardura-2; Cardura-4; Carduran; Diblocin; Doxazosin mesylate; Normothen; Supressin
PharmGKB Accession Id:	PA449407

Description

A selective alpha-1-adrenergic blocker that lowers serum cholesterol. It is also effective in the treatment of hypertension. [PubChem]

Indication

For treatment and management of Hypertension and urinary obstruction symptoms of BPH.

ATC Therapeutic Category

• C02CA:Alpha-adrenoreceptor antagonists

Pharmacology and Interactions

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.

Pharmacology

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 alpha1c 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.

Food Interactions

Avoid alcohol. Avoid natural licorice. Take without regard to meals.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic.

Protein Binding

98%

Absorption

65%

Half Life

22 hours

Toxicity

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

Chemical Properties

Chemical Formula:

C₂₃H₂₅N₅O₅

SMILES Code:

COc1cc2c(cc1OC)nc(nc2N)N3CCN(CC3)C(=O)C4COc5ccccc5O4

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

451.4751 / 451.1856

Curated Annotations ()

1. rs5065 at chr1:11828655 in CLCN6, NPPA
   This variant has been associated with modification of antihypertensive medication effects on blood pressure and cardiovascular disease.

   Variant Name:

   NPPA:T2238C

   Related Drugs:

   amlodipine, chlorthalidone, doxazosin, lisinopril

   Related Diseases:

   Cardiovascular Diseases, Coronary Disease, Stroke

   Evidence:

   PMID:18212314
   

Curated Information

The following genes are in curated knowledge about this drug.

	Gene	Relationship	Evidence
	ACE	PD       GN	Publications
	ADD1	CO          GN	Publications
	CLCN6		Variants
	NPPA	CO          GN	Publications, Variants

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

• ADRA1B
• ADRA1A
• ADRA1D

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

tadalafil	Risk of significant hypotension with this association
vardenafil	Risk of significant hypotension with this association

Curated Information

The following diseases are in curated knowledge about this drug.

	Disease	Relationship	Evidence
	Cardiovascular Diseases	CO          GN	Publications, Variants
	Coronary Disease	CO          GN	Publications, Variants
	Death	CO          GN	Publications
	Heart Failure	CO          GN	Publications
	Hypertension	CO PD       GN	Publications
	Myocardial Infarction	CO          GN	Publications
	Stroke	CO          GN	Publications, Variants

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

LinkOuts

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.