Sildenafil Pharmacological action and mechanism of action

During sexual stimulation, non-renal anergic non-cholinergic neurons of the corpus cavernosum and vascular endothelial nitric oxide synthase catalyze the synthesis of nitric oxide by L-arginine, which activates guanylate cyclase to cyclize Increased guanosine synthesis, which in turn causes relaxation of the smooth muscle of the corpus cavernosum and smooth muscle of the small artery, and blood is injected into the cavernous sinus of the penis, causing the penis to erect. At the same time, cyclic guanosine monophosphate is further hydrolyzed by phosphodiesterase.

Therefore, in theory, whether it is to increase the activity of guanylate cyclase or inhibit the activity of phosphodiesterase, it can increase the level of cyclic guanosine monophosphate, and contribute to the smooth muscle of the corpus cavernosum and the smooth muscle of the penile arteriole. relaxation. Viagra (sildenafil) enhances the level of cyclic guanosine monophosphate by inhibiting the phosphodiesterase hydrolytic activity without affecting cyclic adenosine monophosphate, thereby increasing the effect of nitric oxide synthase/cyclic guanosine cascade caused by sexual stimulation. Relax the smooth muscle of the cavernous body to achieve the purpose of treating erectile dysfunction.

Approximately 96% of sildenafil and its major circulating metabolites (N-demethylates) bind to plasma proteins, and protein binding rates are independent of total drug concentration. The tissue distribution is good and the volume of distribution (Vd) is 105L. Sildenafil is cleared primarily by the liver microsomal enzyme cytochrome P450 3A4 (CYP 3A4, the main pathway) and cytochrome P450 2C9 (CYP 2C9, a minor pathway).

Its main metabolite (N-desmethylate) has similar PDE selectivity to sildenafil, and its plasma concentration is about 40% of sildenafil, so about 20% of the pharmacological effects of sildenafil come from For its metabolites. The elimination half-life of sildenafil and its metabolites is about 4 hours, 80% of the dose is mainly excreted in the form of metabolites by feces, and 13% is excreted by the kidneys. 90 minutes after the administration of the healthy volunteers, the amount of sildenafil was determined to be less than 0.001% of the administered amount in the semen.

Related Articles ：

• Side effects and side effects of sildenafil
• Usage and dosage of sildenafil