PARADOXICAL EFFECTS OF THIORIDAZINE ON ELECTROMECHANICAL COUPLING IN THE HUMAN AND RAT VAS-DEFERENS

The effects of thioridazine on the responses of isolated human and rat vas deferens to high [K+]0, A23187 and caffeine were examined. In the presence of Ca2+ (2.5 mM), thioridazine (1-10-mu-M) induced spontaneous contractions but caused a dose-related inhibition of the phasic and secondary parts of the response to high [K+]0 (136 mM). The relaxation phase of the high [K+]0 response of the human vas deferens was unaffected by thioridazine (up to 10-mu-M). In Ca2+-free/EGTA (0.5 mM) media, thioridazine caused a dose-related potentiation, shortened the latency and prolonged the duration of high [K+]0 responses. Contractions to caffeine (20 mM) and A23187 (20-50-mu-M) were relatively unchanged by thioridazine (10-mu-M). The spontaneous activity caused by thioridazine (10-mu-M) was sensitive to the Ca2+-channel blockers nifedipine (10-mu-M) or verapamil (10-mu-M). These results indicate that the action of thioridazine during electromechanical coupling in the human and rat vas deferens may involve more than its blockade of voltage gated Ca2+ channels.