A mechanism of the potentiation of penile tumescence by T-1032, a new potent and selective phosphodiesterase type V inhibitor, in dogs

• Published in: Japanese Journal of Pharmacology Vol. 82; no. suppl.1; p. 216
• Main Authors: Tsunehisa Noto, Hirotaka Inoue, Tomihiro Ikeo, Kohei Kikkawa
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 2000
• ISSN: 0021-5198; 1347-3506

T-1032, an isoquinolone derivative, is a new selective phosphodiesterase type V (PDE V) inhibitor with nanomolar potency. A mechanism of the potentiation of canine penile tumescence by T-1032 was examined. [in vivo] Pelvic nerve stimulation (PNS) induced a penile tumescence frequency-dependently together with the increase of total nitric-oxide metabolite levels within the corpus cavernosa of anesthetized dogs. Intravenous treatment with T-1032 (1-100 μg/kg) dose-dependently potentiated the tumescence. The potency of T-1032 was equivalent to that of sildenafil. Topical treatment with T-1032 into the corpus cavernosum (one-fiftieth the dose of systemic injection) also potentiated the PNS-induced tumescence. Intravenous T-1032 augmented the tumescence induced by intracavernous injection of sodium nitroprusside (SNP) but not by vasoactive intestinal polypeptide (VIP). [in vitro] In isolated canine corpus cavernosa precontracted by phenylephrine, SNP (0.1-100 μM) or VIP (0.01-1 μM) produced a dose-dependent relaxation accompanied by the increase in cGMP or cAMP levels, respectively. T-1032 (0.01-1 μM) augmented the relaxation induced by SNP but not by VIP. These data suggest that T-1032 caused a potentiation of tumescence through the selective inhibition of PDE V which was located in the smooth muscles of corpus cavernosa.