Comparison of pre- and postsynaptic .ALPHA.-adrenoceptor blocking effects of E-643 in the isolated vas deferens of the rat.

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Abstract
The effectiveness of E 643, a newly developed .alpha.-blocker with potent antihypertensive activity and 4 .alpha.-antagonists in blocking pre- and postsynaptic .alpha.-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 .alpha.-antagonists. The order of affinity (pA2) for presynaptic .alpha.-receptors, as assessed from parallel shift of the dose-response curve to clonidine, was: phentolamine > yohimibne > tolazoline > E-643 .gtoreq. prazosin. At concentrations from 10-8-10-6 M, neither E-643 nor prazosin had any effect on the twitch which had been depressed by the treatment with clonidine; phentolamine, yohimbine and tolazoline partially reversed it. Contractile effects of cumulative concentrations of noradrenaline were also antagonized by .alpha.-antagonists. The order of affinity (pA2) for postsynaptic .alpha.-receptors was: E-643 .gtoreq. prazosin > phentolamine > yohimbine > tolazoline. Selectivity for pre- vs. postsynaptic .alpha.-receptors was assessed by comparing KB values for pre- and postsynaptic .alpha.-receptors. The order of selectivity for the presynaptic .alpha.-receptors was : yohimbine > tolazoline > phentolamine .mchgt. prazosin .gtoreq. E-643. E-643 is a potent and highly selective postsynaptic .alpha.-blocker.