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Viagra (Sildenafil Citrate)

Pfizer Inc. · FDA-approved approved Small molecule Quality 63/100

Sildenafil inhibits phosphodiesterase type 5 to increase cGMP levels, enabling smooth muscle relaxation and penile blood inflow.

Sildenafil is a PDE5 inhibitor indicated for erectile dysfunction treatment that works by enhancing nitric oxide effects to increase penile blood flow. The drug has moderate bioavailability (41%) with rapid absorption and approximately 4-hour half-life, primarily metabolized hepatically via CYP3A4. Major risks include severe hypotension when combined with nitrates or alpha-blockers, and increased exposure with CYP3A4 inhibitors requiring dose adjustments. Clinical use requires careful patient selection and monitoring for drug interactions, particularly with cardiovascular agents.

At a glance

Generic nameSildenafil Citrate
SponsorPfizer Inc.
Drug classPhosphodiesterase-5 (PDE5) inhibitor
TargetPhosphodiesterase type 5 (PDE5)
ModalitySmall molecule
PhaseFDA-approved

Mechanism of action

Sildenafil enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum. During sexual stimulation, NO is released in the corpus cavernosum and activates guanylate cyclase, increasing cGMP levels. By inhibiting PDE5, sildenafil causes increased cGMP accumulation, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum and has no effect in the absence of sexual stimulation at recommended doses. In vitro studies demonstrate that sildenafil is highly selective for PDE5, with approximately 4,000-fold selectivity compared to PDE3 (involved in cardiac contractility). However, sildenafil is only about 10-fold more potent for PDE5 compared to PDE6, an enzyme found in the retina involved in the phototransduction pathway, which is thought to be the basis for color vision abnormalities.

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Primary sources

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SourceUsed for
ClinicalTrials.govTrial enrolment, design, endpoints, results
FDA Orange BookPatents + exclusivity

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