API Pharmaceutical powder cas 139755-83-2 Sildenafi Citrate

cas 139755-83-2 Sildenafi Citrate

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The introduction of Sildenafi

Sildenafi is a white crystalline powder with the molecular formula of c22h30n6o4s and the density of 1.39g/cm3. It is a drug for the treatment of male erectile dysfunction accidentally invented when developing drugs for the treatment of cardiovascular diseases. It is generally known by its commercial name . However, compared with the trade name sildenafi, the common name "" in China is more widely used and has greater influence.

This product is an oral drug for the treatment of penile erectile dysfunction (ED). It is the citrate of sildenafi, a selective inhibitor of phosphodiesterase type 5 (PDE5) specific for cyclic guanosine monophosphate (CGMP). Mechanism of action: the physiological mechanism of penile erection involves the release of nitric oxide (no) in penile sponge during sexl stimulation. No activates guanylate cyclase, which leads to the increase of cyclic guanosine phosphate (CGMP) level, relaxation of smooth muscle and filling of blood in sponge.

Effect of sildenafi on penile erectile response: sildenafi is a highly selective phosphodiesterase 5 (PDE5) inhibitor. PDE5 is highly expressed in penile cavernous body, but low in other tissues (including platelets, blood vessels, visceral smooth muscle and skeletal muscle). Sildenafi can selectively inhibit PDE5, enhance nitric oxide (no) - cGMP pathway and increase cGMP level, resulting in relaxation of penile cavernous smooth muscle, so that patients with erectile dysfunction have a natural erectile response to se stimulation. Erectile response generally increased with the increase of sildenafi dose and plasma concentration. The experiment showed that the efficacy lasted up to 4 hours, but the response was weaker than that in 2 hours. Response of sildenafi to myocardium: PDE5 does not exist in normal or diseased cardiac conduction tissue, cardiomyocytes, endothelial cells and lymphoid tissue. Therefore, sildenafi (PDE5 inhibitor) has no positive inotropic effect and cannot directly affect myocardial contractile function.

Effect of sildenafi on cardiac parameters: normal male volunteers took sildenafi 100mg orally without clinically significant ECG changes. Under the monitoring of Swan Ganz catheter, 8 patients with stable ischemic heart disease were injected with sildenafi with a total amount of 40 mg in four times. Results: at rest, the systolic and diastolic blood pressure decreased by 7% and 10% respectively compared with baseline. Resting right atrium, pulmonary artery pressure, pulmonary wedge pressure and cardiac output decreased by 28%, 28%, 20% and 7% respectively. Although the intravenous dose was 2-5 times higher than the average peak plasma concentration of sildenafi 100mg in healthy male volunteers, the above hemodynamic response still existed during exercise.

Response of sildenafi to blood pressure: a single oral dose of sildenafi 100mg in healthy male patients resulted in a decrease in blood pressure in the lying position (the average maximum range was 8.4 / 5.5mmhg). The blood pressure decreased most significantly 1-2 hours after taking the medicine, and there was no difference with the placebo group 8 hours after taking the medicine. Sildenafi 25mg, 50mg and 100mg had similar effects on blood pressure, which seemed to have nothing to do with drug dose and blood concentration. Patients taking nitrates at the same time had greater antihypertensive effect. Hypotension (90 / 50mmhg) and nitrates or drugs that provide nitrate are strict contraindications to sildenafi. The maximum effect of sildenafi on blood pressure occurred about 1 hour after administration, which was consistent with the peak value of drug plasma. Therefore, sel activity may induce cardiac events at the peak plasma concentration of sildenafi. Although the hypotension response caused by sildenafi is mild and transient (blood pressure returns to baseline within 4 hours), the interaction between sildenafi and nitrates can produce significant and longer-term blood pressure reduction. Sildenafi has a short half-life and can be eluted within 24 hours (about 6 half-lives). The American College of Cardiology and the American Heart Association have made it clear that sildenafi is prohibited for those who have used nitrates within 24 hours.

Effect of sildenafi on vision: studies have shown that when taking drugs twice the maximum recommended dose, this product has no effect on vision, electroretinogram, intraocular pressure and nipple size. There may be a transient Blue / green color discrimination abnormality. Whether used alone or in combination with aspirin, this product has no effect on human bleeding time. In vitro experiments, this product enhances the anti human platelet aggregation effect of sodium nitroprusside (NO donor). In anesthetized rabbits, the combination of heparin and sildenafi has a superimposed effect on the prolongation of bleeding time, but no similar human study has been carried out. After taking sildenafi 100mg orally, the motility and morphology of sperm in healthy volunteers were not affected.

Sildenafi is a selective inhibitor of cyclic guanosine monophosphate (CGMP) - specific type 5 phosphodiesterase (PDE5). It is an oral drug for the treatment of ED. The physiological mechanism of normal penile erection involves the release of nitric oxide (no) during sel stimulation. Nitric oxide activates guanylate cyclase in penile cavernous smooth muscle cells, resulting in the increase of cGMP level, relaxation of smooth muscle in sponge body, expansion of cavernous sinus, blood inflow and penile erection. Patients with erectile dysfunction are mainly due to the relaxation of smooth muscle of corpus cavernosum. Sildenafi has no direct relaxation effect on isolated human sponge, but can enhance the effect of nitric oxide by inhibiting the decomposition of cGMP by PDE5 in sponge. When sl stimulation causes the release of local nitric oxide, sildenafi inhibits PDE5, which can increase the level of cGMP in the sponge, relax the smooth muscle of the sponge and flow blood into the sponge. Studies have shown that the erectile response increases with the increase of dose and plasma concentration, and the efficacy can last for 4H (but weaker than 2H). In vitro experiments showed that sildenafi had high selectivity for PDE5, which was more than 80 times that of pde1, 700 times that of PDE2 and PDE4, and 4000 times that of PDE3. Since PDE3 is related to the control of myocardial contractility and there is no PDE5 in myocardium, sildenafi has no positive inotropic effect and does not directly affect myocardial contractile function. However, sildenafi can relax systemic circulation vessels. Oral administration of large dose (100mg) can lead to the decrease of lying position blood pressure [average maximum decrease of 1.12/0.73kpa (8.4 / 5.5mmhg)], and the decrease of blood pressure is the most obvious 1 ~ 2H after taking the medicine. Therefore, sl activity may induce cardiac events at the peak of blood concentration. The selective effect of sildenafi on PDE5 is only 10 times that on PDE6, which is an enzyme existing in the retina. Therefore, sildenafi may cause color vision abnormalities at high dose or high blood concentration. In addition to human cavernous smooth muscle, low concentrations of PDE5 were also found in platelets, blood vessels, visceral smooth muscle and skeletal muscle. Sildenafi may enhance the effects of antiplatelet aggregation (in vitro), platelet thrombosis (in vivo) and peripheral vasodilation (in vivo) by inhibiting PDE5 in these tissues

Application of Sildenafi

For the treatment of penile erectile dysfunction

COA of Sildenafi