QuickView for Alfuzosin (compound)

Summary
General Info

PubChem

PubChem Compound 2092

Name:	alfuzosin
PubChem Compound ID:	2092
Molecular formula:	C₁₉H₂₇N₅O₄
Molecular weight:	389.449 g/mol
Synonyms:	Alfuzosin; Prestwick1_000322; KBioGR_001616; Spectrum2_000505; N-(3-((4-Amino-6,7-dimethoxy-2-quinazolinyl)methylamino)propyl)tetrahydro-2-furancarboxamide; HSDB 7290; KBio3_001866; 2-Furancarboxamide, N-(3-((4-amino-6,7-dimethoxy-2-quinazolinyl)methylamino)propyl)tetrahydro-; Spectrum4_001208; Spectrum3_001063. show more » Alfuzosin; Prestwick1_000322; KBioGR_001616; Spectrum2_000505; N-(3-((4-Amino-6,7-dimethoxy-2-quinazolinyl)methylamino)propyl)tetrahydro-2-furancarboxamide; HSDB 7290; KBio3_001866; 2-Furancarboxamide, N-(3-((4-amino-6,7-dimethoxy-2-quinazolinyl)methylamino)propyl)tetrahydro-; Spectrum4_001208; Spectrum3_001063; Alfuzosinum [Latin]; SPBio_000429; 81403-68-1; Prestwick0_000322; SL 77499; 81403-80-7; Alfuzosina [Spanish]; SPBio_002244; Alfuzosine [French] show less «

DrugBank

Identification

Name:	alfuzosin
Name (isomeric):	DB00346
Drug Type:	small molecule
Synonyms:	Alfusosine
Brand:	Xatral, Uroxatral
Category:	Adrenergic alpha-Antagonists, Antihypertensive Agents
CAS number:	81403-80-7

Pharmacology

Indication:	For the reduction of urinary obstruction and relief of associated manifestations (eg. sensation of incomplete bladder emptying or straining, urgency, interrupted or weak stream) in patients with symptomatic beningn prostatic hyperplasia.
Pharmacology:	Alfuzosin is a quinazoline-derivative alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Accordingly, alfuzosin is a selective inhibitor of the alpha(1) subtype of alpha adrenergic receptors. In the human prostate, alfuzosin antagonizes phenylephrine (alpha(1) agonist)-induced contractions, in vitro,... show more » Alfuzosin is a quinazoline-derivative alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Accordingly, alfuzosin is a selective inhibitor of the alpha(1) subtype of alpha adrenergic receptors. In the human prostate, alfuzosin antagonizes phenylephrine (alpha(1) 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 alfuzosin competitively antagonized the pressor effects of phenylephrine (an alpha(1) agonist) and the systolic pressor effect of norepinephrine. The antihypertensive effect of alfuzosin results from a decrease in systemic vascular resistance and the parent compound alfuzosin is primarily responsible for the antihypertensive activity. show less «
Mechanism of Action:	Alfuzosin is a non-subtype specific alpha(1)-adrenergic blocking agent that exhibits selectivity for alpha(1)-adrenergic receptors in the lower urinary tract. Inhibition of these adrenoreceptors leads to the relaxation of smooth muscle in the bladder neck and prostate, resulting in the improvement in urine flow and a reduction in symptoms in benign... show more » Alfuzosin is a non-subtype specific alpha(1)-adrenergic blocking agent that exhibits selectivity for alpha(1)-adrenergic receptors in the lower urinary tract. Inhibition of these adrenoreceptors leads to the relaxation of smooth muscle in the bladder neck and prostate, resulting in the improvement in urine flow and a reduction in symptoms in benign prostate hyperplasia. Alfuzosin also inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation. show less «
Absorption:	Absorption is 50% lower under fasting conditions
Protein binding:	82%-90%
Biotransformation:	Hepatic. Alfuzosin undergoes extensive metabolism by the liver, with only 11% of the administered dose excreted unchanged in the urine. Alfuzosin is metabolized by three metabolic pathways: oxidation, O-demethylations, and N-dealkylation. The metabolites are not pharmacologically active. CYP3A4 is the principal hepatic enzyme isoform involved in its metabolism.
Route of elimination:	Following oral administration of 14C-labeled alfuzosin solution, the recovery of radioactivity after 7 days (expressed as a percentage of the administered dose) was 69% in feces and 24% in urine.
Half Life:	10 hours
Toxicity:	Side effects are dizziness (due to postural hypotension), upper respiratory tract infection, headache, and fatigue.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Take after a meal (always the same meal), product bioavailability is reduced when taken on an empty stomach.

Drug interaction:

Tamsulosin	Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Alfuzosin, may result in additive antihypertensive effects. Combination therapy is not recommended.
Ritonavir	Ritonavir increases the effect/toxicity of alfuzosin
Itraconazole	The antifungal increases the effect of alfuzosin
Conivaptan	CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Concomitant use of alfuzosin with a strong CYP3A4 inhibitor is a listed contraindication according to alfuzosin prescribing information.
Terazosin	Additive antihypertensive effects may occur. Increase risk of orthostatic hypotension and syncope. Concomitant therapy should be avoided.

Targets

Alpha-1A adrenergic receptor

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

UniProt ID:

P35348

Gene:

ADRA1A

Actions:

antagonist

References:

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
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Kenny BA, Miller AM, Williamson IJ, O'Connell J, Chalmers DH, Naylor AM: Evaluation of the pharmacological selectivity profile of alpha 1 adrenoceptor antagonists at prostatic alpha 1 adrenoceptors: binding, functional and in vivo studies. Br J Pharmacol. 1996 Jun;118(4):871-8.
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Lee M: Alfuzosin hydrochloride for the treatment of benign prostatic hyperplasia. Am J Health Syst Pharm. 2003 Jul 15;60(14):1426-39.
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Andersson KE, Lepor H, Wyllie MG: Prostatic alpha 1-adrenoceptors and uroselectivity. Prostate. 1997 Feb 15;30(3):202-15.
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Lowe FC: Role of the newer alpha, -adrenergic-receptor antagonists in the treatment of benign prostatic hyperplasia-related lower urinary tract symptoms. Clin Ther. 2004 Nov;26(11):1701-13.
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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.
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Faure C, Pimoule C, Vallancien G, Langer SZ, Graham D: Identification of alpha 1-adrenoceptor subtypes present in the human prostate. Life Sci. 1994;54(21):1595-605.
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Beique L, Por CP, Evans MF: Are the new selective alpha-blockers better than non-selective alpha-blockers for benign prostatic hyperplasia? Can Fam Physician. 1998 Dec;44:2659-62.
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McVary KT: BPH: epidemiology and comorbidities. Am J Manag Care. 2006 Apr;12(5 Suppl):S122-8.
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Elhilali MM: Alfuzosin: an alpha1-receptor blocker for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Expert Opin Pharmacother. 2006 Apr;7(5):583-96.
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Roehrborn CG: Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker. Urology. 2001 Dec;58(6 Suppl 1):55-63; discussion 63-4.
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Alpha-1B adrenergic receptor

Alpha-1D adrenergic receptor

Enzymes

Cytochrome P450 3A4