The history of sildenafil

Sildenafil was developed by Pfizer Inc. of the United States and was first introduced into clinical research as a 5-phosphodiesterase inhibitor for the treatment of cardiovascular diseases.

The researchers hope that sildenafil can relax the blood vessels and relieve cardiovascular disease by releasing the bioactive substance nitric oxide to relax the cardiovascular smooth muscle. But clinical studies have shown that the cardiovascular effects of sildenafil do not meet the researchers' expectations. As a cardiovascular drug, sildenafil is disappointing and cannot grow into a successful treatment.

In April 1991, the clinical study of sildenafil officially failed, but a side effect reported by the subjects caught the attention of the researchers. The researchers found that the healers were reluctant to hand over the remaining drugs after receiving the test. Under investigation, it was found that this medicine improved the sexual life of the patient. After permission from Pfizer's high-level, the researchers conducted a study on the effect of sildenafil on the corpus cavernosum smooth muscle, and on March 27, 1998, obtained the US Federal Food and Drug Administration's marketing approval, becoming the reputation of Pfizer. A product of great noise.

Sildenafil was the first oral anti-cancer drug listed in the United States in April 1998. Many studies have proven. Nitric oxide (NO) is the main mediator of smooth muscle relaxation and erection of the cavernous body.

Sildenafil is a selective inhibitor of phosphodiesterase (PDE) V, which enhances the physiological response of penile erection caused by NO release under sexual stimulation.

NO is released from nerve endings and endothelial cells to bind to receptors on the smooth muscle of the cavernous body, and activates intracellular soluble guanylate cyclase, which in the presence of Mn2+ promotes the conversion of guanosine triphosphate (GTP) to cyclodextrose. Guanosine (cGMP), cGMP-activated protein kinase G (PKG) and a small fraction of protein kinase A (PKA), activated PKG and PKA reduce intracellular free Ca2+ levels by activating Ca2+ pumps, resulting in relaxation of cavernosal smooth muscle, arterial blood Inflow, penile congestion, hard, erection.

The presence of PDE V in human cavernous tissue and vascular smooth muscle can hydrolyze cGMP to GMP and block the NO-cGMP pathway that causes the penis to erect. Sildenafil is a selective inhibitor of PDE V, which prevents the degradation of cGMP and thus enhances the penile erection of sexual excitement. In vitro tests have shown that sildenafil has a greater selectivity for PDE V than other isozymes of PDE. It has no effect on PDEIII involving cardiac contraction, but inhibits PDEVI present in the retina at higher doses, affecting vision. Bottles are hard to buy in the country that is imported from the United States.