PURPOSE: Intracavernous injection of prostaglandin (PG) E1 or papaverine (PA) is widely used in the diagnosis and treatment of erectile dysfunction. Because these drugs are sometimes associated with insufficient erection in and side effects such as priapism, corporal fibrosis, and pain, there has been increasing interest in finding effective and safe alternatives. Recent studies demonstrated that pinacidil (PI) relaxes the smooth muscle. This study was performed to examine the efficacy of PI as an alternative or supplement to drugs such as PG, PA, or phentolamine (PT). MATERIALS AND METHODS: In 28 adult male cats, the maximal intracavernous pressure (ICPmax), time to ICPmax (T1/2) and duration of increased ICP (time) in response to intracavernous injection of PG, PA, or mixture of vasoactive drugs (PA + PT, PA + PG + PT) were compared with the responses to mixtures containing PI (PI + PA, PI + PA + PT, PI + PG + PA). The same concentration of drug (10-10 - 10-6M) was used in all cocktails. RESULTS: All double- and triple-drug mixtures exhibited a synergistic erectile effect on the penis. Among the triple mixtures, PI + PG + PT and PI + PG + PA were more effective and less harmful than the PA + PG + PT (p<0.01). Cocktails including PI had a shorter T1/2 than the others (p<0.05). Cocktails containing PA had significantly longer Time than the others (p<0.05). CONCLUSIONS: Pinacidil may be useful as an alternative or supplement to drugs now in use for intracavernous injection. Cocktails such as PI + PG or PI + PG + PT seem promising for patients who cannot achieve an adequate erection with other agents.