[Pharmacological profiles of sildenafil (VIAGRA) in the treatment of erectile dysfunction: efficacy and drug interaction with nitrate].
Penile erection follows relaxation of the corpus cavernosum in which nitric oxide (NO) released during sexual stimulation from non-adrenergic non-cholinergic nerve endings and from endothelial cells of the corpus cavernosum plays a crucial role. Sildenafil (VIAGRA) selectively inhibited phosphodiesterase type 5 (PDE5) activity in the human corpus cavernosum and increased cGMP concentrations in the rabbit cavernosum in the presence of NO. Sildenafil enhanced the NO-dependent relaxation of the isolated human corpus cavernosum and the intracavernosal pressure in the anesthetized dog without affecting systemic blood pressure and heart rate. In the patients with erectile dysfunction, an orally administered sildenafil enhanced the penile rigidity during visual sexual stimulation. Sildenafil did not affect the phenylephrine-induced contraction of the isolated rabbit aorta, but enhanced the relaxant effect of glyceryl trinitrate. The pharmacodynamic interaction with glyceryl trinitrate was also observed in human studies where sildenafil potentiated the hypotensive effect of the nitrate. These results indicate that sildenafil, which enhances the physiological process of penile erection during sexual arousal, is a novel orally effective treatment for erectile dysfunction. It should be noted, however, that sildenafil enhanced the hypotensive effect of glyceryl trinitrate, as a result of inhibition of PDE5 in vascular smooth muscle. Therefore, administration of sildenafil to patients who are using nitrates and NO donors is contraindicated.
Omote
M
M
Central Research, Pfizer Pharmaceutical Inc., Aichi, Japan. omote@pfizer.co.jp
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D004347:Drug Interactions; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011687:Purines; D011817:Rabbits; D000068677:Sildenafil Citrate; D013450:Sulfones
D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D005996:Nitroglycerin; D006152:Cyclic GMP