Sildenafil-d3 is intended for use as an internal standard for the quantification of sildenafil by GC- or LC-MS. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE5) with IC50 values of 3.6 and 3 nM for PDE5 activity in isolated rabbit platelets and human corpus cavernosum, respectively.1 It is selective for PDE5 over PDE1 and PDE3 (IC50s = 0.26 and 65 μM, respectively). Sildenafil reverses glucose-induced decreases in angiopoietin 1 (Ang1) expression and reduction of capillary-like tube formation by mouse dermal endothelial cells in vitro and increases the number of functional blood vessels and regional blood flow in the sciatic nerve in a db/db mouse model of diabetic peripheral neuropathy.2 It increases the ratio of maximum intracavernosal pressure to mean arterial blood pressure (ICP/MAP), a measure of erectile function, in castrated rats when administered at a dose of 20 mg/kg per day.3 Sildenafil (0.5 mg/kg) also reduces cardiac arrest and resuscitation-induced increases in angiotensin II , angiotensin converting enzyme (ACE), ACE2, and various angiotensin receptors and increases survival in a porcine model of ischemia/reperfusion injury.4 Formulations containing sildenafil have been used in the treatment of erectile dysfunction, pulmonary arterial hypertension, and high-altitude pulmonary edema associated with altitude sickness.
1.Terrett, N.K., Bell, A.S., Brown, D., et al.Sildenafil (ViagraT), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunctionBioorganic & Medicinal Chemistry Letters6(15)1819-1824(1996) 2.Wang, L., Chopp, M., Szalad, A., et al.Sildenafil ameliorates long term peripheral neuropathy in type II diabetic micePLoS One10(2)e0118134(2015) 3.Mulhall, J.P., Verma, N., Deveci, S., et al.Sildenafil citrate improves erectile function after castration in a rat modelBJU Int.113(4)656-661(2014) 4.Wang, G., Zhang, Q., Yuan, W., et al.Sildenafil protects against myocardial ischemia-reperfusion injury following cardiac arrest in a porcine model: Possible role of the renin-angiotensin systemInt. J. Mol. Sci.16(11)27015-27031(2015)