COMPARISON OF PRE- AND POSTSYNAPTIC α-ADRENOCEPTOR BLOCKING EFFECTS OF E-643 IN THE ISOLATED VAS DEFERENS OF THE RAT

Abstract

AbstractEffectiveness of E-643, a newly developed α-blocker, and four α-antagonists in blocking pre- and postsynaptic α-adrenoceptors were compared in the isolated rat vas deferens. The inhibitory effect of Clonidine on the field-stimulated twitch response was antagonized in the presence of the α-antagonists. The order of affinity (pA2) for presynaptic α-receptors, as assessed from parallel shift of the dose-response curve to Clonidine, was: phentolamine>yohimbine>tolazoline>E-643≥prazosin. At concentrations from 10−8 to 10−6 M, neither E-643 nor prazosin had any effect on the twitch which had been depressed by the treatment with Clonidine, whereas phentolamine, yohimbine and tolazoline partially reversed it. Contractile effects of cumulative concentrations of noradrenaline were also antagonized by α-antagonists. The order of affinity (pA2) for postsynaptic α-receptors was: E-643≥prazosin>phentolamine>yohimbine> tolazoline. Selectivity for pre- versus postsynaptic α-receptors was assessed by comparing KB values for pre- and postsynaptic α-receptors. The order of selectivity for the presynaptic α-receptors was : yohimbine>tolazoline>phentolamine>>prazosin≥E-643. It is concluded that E-643 is a potent and highly selective postsynaptic α-blocker.