QuickView for Sildenafil (compound)

Summary
General Info

PubChem

PubChem Compound 5212

Name:	sildenafil
PubChem Compound ID:	5212
Molecular formula:	C₂₂H₃₀N₆O₄S
Molecular weight:	474.578 g/mol
Synonyms:	KBio2_007171; 171599-83-0; 1-((3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine; KBio3_002927; Spectrum2_001648; DivK1c_006894; KBio1_001838; BAS 04213629; Spectrum3_001892; VIA. show more » KBio2_007171; 171599-83-0; 1-((3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine; KBio3_002927; Spectrum2_001648; DivK1c_006894; KBio1_001838; BAS 04213629; Spectrum3_001892; VIA; Spectrum4_000586; Sildenafil Viagra; KBio2_004603; Spectrum_001555; SpecPlus_000798; KBio2_002035; KBioGR_001052; Piperazine, 1-((3-(4,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methyl-; KBioSS_002035; 139755-83-2; LS-111655; Sildenafil; C07259; SPBio_001775 show less «

DrugBank

Identification

Name:	sildenafil
Name (isomeric):	DB00203
Drug Type:	small molecule
Synonyms:	Sildenafil Citrate
Brand:	Revatio, Viagra
Category:	Vasodilator Agents, Phosphodiesterase Inhibitors
CAS number:	139755-83-2

Pharmacology

Indication:	For the treatment of erectile dysfunction and to relieve symptoms of pulmonary arterial hypertension (PAH).
Pharmacology:	Erections are controlled by the parasympathetic nervous system. Upon sexual stimulation, a decrease in vascular resistance is mediated by acetylcholine and nitric oxide resulting in vasodilation. The hemodynamic mechanism of an erection is comprised of five stages. During the latent stage, arterial and carvernous smooth muscle relaxation occurs. Va... show more » Erections are controlled by the parasympathetic nervous system. Upon sexual stimulation, a decrease in vascular resistance is mediated by acetylcholine and nitric oxide resulting in vasodilation. The hemodynamic mechanism of an erection is comprised of five stages. During the latent stage, arterial and carvernous smooth muscle relaxation occurs. Vasodilation results in high levels of blood flow causing the penis to grow to its full size. This stage is called tumescence. During the full-erection stage, blood flow fills penis sinusoids and outflow is restricted. This is followed by the rigid-erection phase during which the cavernous muscles contract causing the penis to become rigid. Little blood flow occurs during this stage. During the final stage, detumescence, the cavernous muscles relax and blood flows out of the penis. Erectile dysfunction may occur when there is insufficient blood supply to the penis or when the penis is unable to prevent outflow of blood from the penis. Sildenafil is a specific inhibitor of PDE5, an enzyme responsible for the breakdown of cGMP to 5’-GMP. Increased levels of cGMP stimulate vasodilation and facilitate the generation and maintenance of erections. These vasodilatory effects also help decrease symptoms of PAH. Sildenfail also exhibits some activity against PDE6 (10 times less potentcy compared to PDE5), a PDE isoform found predmoninantly in the retina. This activity is responsible for the blue tinged vision experienced by users of sildenafil. show less «
Mechanism of Action:	Sildenafil inhibits the cGMP-specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response i... show more » Sildenafil inhibits the cGMP-specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by sildenafil enhances erectile function by increasing the amount of cGMP. show less «
Absorption:	>90% absorbed with ~40% reaching systemic circulation unchanged following first-pass metabolism
Protein binding:	96%
Biotransformation:	Sildenafil appears to be completely metabolized in the liver to 16 metabolites. Its metabolism is mediated mainly by cytochrome P450 microsomal isozymes 3A4 (major route) and 2C9 (minor route). The major circulating metabolite, N-demethylated metabolite, has PDE selectivity similar to the parent drug and ~50% of its in vitro potency. The N-demethylated metabolite is further metabolized to an N-dealkylated N,N-de-ethylated metabolite. Sildenafil also undergoes N-dealkylation followed by N-demethylation of the piperazine ring.
Route of elimination:	Sildenafil is cleared predominantly by the CYP3A (major route) and cytochrome P450 2C9 (CYP2C9, minor route) hepatic microsomal isoenzymes. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose).
Half Life:	4 hours
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Ciprofloxacin	Ciprofloxacin may increase the serum level of sildenafil.
Indinavir	The protease inhibitor, indinavir, may increase the effect and toxicity of sildenafil.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of sildenafil by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of sildenafil if voriconazole is initiated, discontinued or dose changed.
Amprenavir	The protease inhibitor, amprenavir, may increase the effect and toxicity of sildenafil.
Telithromycin	Telithromycin may reduce clearance of Sildenafil. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Sildenafil if Telithromycin is initiated, discontinued or dose changed.

Ciprofloxacin	Ciprofloxacin may increase the serum level of sildenafil.
Indinavir	The protease inhibitor, indinavir, may increase the effect and toxicity of sildenafil.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of sildenafil by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of sildenafil if voriconazole is initiated, discontinued or dose changed.
Amprenavir	The protease inhibitor, amprenavir, may increase the effect and toxicity of sildenafil.
Telithromycin	Telithromycin may reduce clearance of Sildenafil. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Sildenafil if Telithromycin is initiated, discontinued or dose changed.
Pentaerythritol Tetranitrate	Possible significant hypotension with this combination
Nelfinavir	The protease inhibitor, nelfinavir, may increase the effect and toxicity of sildenafil.
Nitroglycerin	Possible significant hypotension with this combination
Itraconazole	Itraconazole may increase the effect and toxicity of sildenafil.
Ketoconazole	Ketoconazole may increase the effect and toxicity of sildenafil.
Terazosin	Increased risk of hypotension.
Clarithromycin	Increases the effect and toxicity of sildenafil
Fosamprenavir	The protease inhibitor, fosamprenavir, may increase the effect and toxicity of sildenafil.
Atazanavir	Increases the effect and toxicity of sildenafil
Erythromycin	The macrolide, erythromycin, may increase the effect and toxicity of sildenafil.
Tipranavir	Tipranavir, co-administered with Ritonavir, may increase the concentration of Sildenafil. Alternate therapy should be considered.
Cimetidine	Increases the effect and toxicity of sildenafil
Conivaptan	CYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Sildenafil. When sildenanfil is used for treatment of pulmonary arterial hypertension, concurrent use with strong CYP3A4 inhibitors is not recommended. When sildenafil is used for treatment of erectile dysfunction, consider using a lower starting dose of 25 mg in patients who are also taking a strong CYP3A4 inhibitor. Due to the particularly strong effects of ritonavir, sildenafil (for erectile dysfunction) doses greater than 25 mg per 48 hours are not recommended. Of note, the interaction between CYP3A4 inhibitors and sildenafil is predicted to be greater with orally administered than with injected sildenafil.
Isosorbide Dinitrate	Possible significant hypotension with this combination
Isosorbide Mononitrate	Possible significant hypotension with this combination

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Targets

cGMP-specific 3',5'-cyclic phosphodiesterase

Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma

Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma

Enzymes

Transporters

Multidrug resistance-associated protein 4

Multidrug resistance-associated protein 5

Multidrug resistance-associated protein 7