Sildenafil is a research liquid that is an inhibitor of type 5 phosphodiesterase (PDE5) that produces arterial smooth muscle relaxation leading to vasodilation in the penis and the lungs of animal test subjects.

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WHAT IS SILDENAFIL CITRATE?

Sildenafil is a selective phosphodiesterase type 5 (PDE5) inhibitor which prolongs the activation of cyclic guanosine monophosphate (cGMP), a major mediator of the vasodilatory action of nitric oxide (NO). Inhibition of PDE5 leads to prolongation of smooth muscle relaxation in the corpus cavernosum of the penis (improving erections) and in the pulmonary vasculature (decreasing pulmonary artery pressure).

STRUCTURE OF SILDENAFIL

IUPAC Name: 5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-1-methyl-3-propyl-6H-pyrazolo[4,3-d]pyrimidin-7-one;2-hydroxypropane-1,2,3-tricarboxylic acid

Molecular Formula: C₂₈H₃₈N₆O₁₁S

Molecular weight: 666.7 g/mol

CAS number: 171599-83-0

MECHANISM OF ACTION

Sildenafil is primarily metabolized by cytochrome p450 3A4. Inhibitors of this enzyme (macrolide antibiotics, antifungals, cimetidine) may increase sildenafil serum concentrations enhancing pharmacological and toxicological effects.

SILDENAFIL EFFECTS

Across all trials in animal test subjects, sildenafil demonstrated a variety of benefits. They include the following:

• It is beneficial in managing pulmonary arterial hypertension
• It increases bladder and prostate tissue oxygenation.
• It improves benign prostatic hyperplasia.
• It improves cognitive function in animals with hepatic encephalopathy.
• It reverses cardiac remodeling in animal models of heart failure.
• It improves erectile dysfunction.
• It improves endothelial function and placental perfusion in preeclamptic patients.
• It reduces inflammation, offering therapeutic potential in bronchial asthma.
• It is effective in treating lower urinary tract symptoms.

SILDENAFIL SIDE EFFECTS

Common side effects include:

• Dizziness
• Headache
• Flushing
• Hypotension
• Rhinitis
• Dyspepsia
• Vision and hearing loss
• Hypotension
• Priapism.

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References:

1. Muirhead GJ, Wulff MB, Fielding A, Kleinermans D, Buss N. Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir. Br J Clin Pharmacol. 2000 Aug;50(2):99-107. – PMC – PubMed

2. Corbin JD. Mechanisms of action of PDE5 inhibition in erectile dysfunction. Int J Impot Res. 2004;16 Suppl 1:S4–S7. doi:10.1038/sj.ijir.3901205

3. Boolell M et al. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996; 8: 47–52.

4. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Sildenafil. [Updated 2017 Aug 2]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548510/

1. Goldstein I, Burnett AL, Rosen RC, Park PW, Stecher VJ. The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction. Sex Med Rev. 2019 Jan;7(1):115-128. – PubMed.