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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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Doxazosin mesilate
  • Doxazosin mesylate
Brand names
  • Alfadil (Pfizer (Sweden))
  • Cardenalin (Pfizer (Japan; discontinued))
  • Cardular (Pfizer (Germany))
  • Cardura (Pfizer)
  • Cardura XL (Pfizer)
  • 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 mixtures Not Available
Categories
  • Antineoplastic Agents
  • Antihypertensive Agents
  • Vasodilator Agents
  • Adrenergic alpha-Antagonists
  • Alpha-adrenergic Blocking Agents
  • Antihyperplasia Agents
CAS number 74191-85-8
Weight Average: 451.4751
Monoisotopic: 451.185568935
Chemical Formula C23H25N5O5
InChI Key InChIKey=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)
Plain Text
IUPAC Name
2-{4-[(2,3-dihydro-1,4-benzodioxin-2-yl)carbonyl]piperazin-1-yl}-6,7-dimethoxyquinazolin-4-amine
SMILES
COC1=CC2=C(C=C1OC)C(N)=NC(=N2)N1CCN(CC1)C(=O)C1COC2=C(O1)C=CC=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Quinazolines
Substructures
  • Quinazolines
  • Phenols and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Piperazines
  • Ethers
  • Benzene and Derivatives
  • Pyrimidines and Derivatives
  • Catechols
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Cyanamides
  • Phenyl Esters
Pharmacology
Indication For treatment and management of mild to moderate hypertension and urinary obstruction symptoms caused by BPH.
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 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.
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.
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
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
Dosage forms
Form Route Strength
Tablet Oral 1 mg
Tablet Oral 2 mg
Tablet Oral 4 mg
Tablet Oral 8 mg
Tablet, extended release Oral 4 mg
Tablet, extended release Oral 8 mg
Prices
Unit description Cost Unit
Cardura XL 4 mg 24 Hour tablet 2.22 USD tablet
Cardura xl 8 mg tablet 2.04 USD tablet
Cardura xl 4 mg tablet 1.94 USD tablet
Cardura 8 mg tablet 1.93 USD tablet
Cardura 4 mg tablet 1.89 USD tablet
Cardura 2 mg tablet 1.81 USD tablet
Cardura 1 mg tablet 1.72 USD tablet
Doxazosin mesylate 8 mg tablet 1.04 USD tablet
Cardura 4 mg Tablet 1.0 USD tablet
Doxazosin mesylate 4 mg tablet 0.99 USD tablet
Doxazosin mesylate 1 mg tablet 0.94 USD tablet
Doxazosin mesylate 2 mg tablet 0.94 USD tablet
Cardura 2 mg Tablet 0.77 USD tablet
Cardura 1 mg Tablet 0.64 USD tablet
Apo-Doxazosin 4 mg Tablet 0.56 USD tablet
Mylan-Doxazosin 4 mg Tablet 0.56 USD tablet
Novo-Doxazosin 4 mg Tablet 0.56 USD tablet
Pms-Doxazosin 4 mg Tablet 0.56 USD tablet
Apo-Doxazosin 2 mg Tablet 0.43 USD tablet
Mylan-Doxazosin 2 mg Tablet 0.43 USD tablet
Novo-Doxazosin 2 mg Tablet 0.43 USD tablet
Pms-Doxazosin 2 mg Tablet 0.43 USD tablet
Apo-Doxazosin 1 mg Tablet 0.36 USD tablet
Mylan-Doxazosin 1 mg Tablet 0.36 USD tablet
Novo-Doxazosin 1 mg Tablet 0.36 USD tablet
Pms-Doxazosin 1 mg Tablet 0.36 USD tablet
Patents Not Available
Properties
State solid
Melting point 289-290oC
Experimental Properties
Property Value Source
water solubility 24 mg/L PhysProp
logP 2.1 PhysProp
Predicted Properties
Property Value Source
water solubility 7.90e-01 g/l ALOGPS
logP 2.53 ALOGPS
logP 2.14 ChemAxon Molconvert
logS -2.76 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 9 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 112.27 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 121.64 ChemAxon Molconvert
polarizability 46.63 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  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
External Links
Resource Link
KEGG Compound C06970 Link_out
PubChem Compound 3157 Link_out
PubChem Substance 46506825 Link_out
ChemSpider 3045 Link_out
ChEBI 4708 Link_out
ChEMBL 4708 Link_out
Therapeutic Targets Database DAP000381 Link_out
PharmGKB PA449407 Link_out
Drug Product Database 2243217 Link_out
RxList http://www.rxlist.com/cgi/generic/doxazo.htm Link_out
Drugs.com http://www.drugs.com/doxazosin.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/car1069.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Doxazosin Link_out
ATC Codes
  • C02CA04
AHFS Codes
  • 24:20.00
PDB Entries Not Available
FDA label show (511 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid natural licorice.
  • Take without regard to meals.
Targets

1. Alpha-1A adrenergic receptor

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Alpha-1B adrenergic receptor

Pharmacological action: yes
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P35368 Link_out
Gene: ADRA1B Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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

3. Alpha-1D adrenergic receptor

Pharmacological action: yes
Actions: antagonist

This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium

Organism class: human
UniProt ID: P25100 Link_out
Gene: ADRA1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

4. Potassium voltage-gated channel subfamily H member 2

Pharmacological action: unknown
Actions: inhibitor

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 delayed rectifying potassium current in heart (IKr). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1

Organism class: human
UniProt ID: Q12809 Link_out
Gene: KCNH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

5. Potassium voltage-gated channel subfamily H member 6

Pharmacological action: unknown
Actions: inhibitor

Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current. Channel properties may be modulated by cAMP and subunit assembly

Organism class: human
UniProt ID: Q9H252 Link_out
Gene: KCNH6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

6. Potassium voltage-gated channel subfamily H member 7

Pharmacological action: unknown
Actions: inhibitor

Pore-forming (alpha) subunit of voltage-gated potassium channel. Channel properties may be modulated by cAMP and subunit assembly

Organism class: human
UniProt ID: Q9NS40 Link_out
Gene: KCNH7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 2C19

Actions: substrate

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

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2D6

Actions: substrate

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
Carriers

1. Alpha-1-acid glycoprotein 1

Appears to function in modulating the activity of the immune system during the acute-phase reaction

UniProt ID: P02763 Link_out
Gene: ORM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:05

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.