Ca2+ channel-blocking effect of the yohimbine derivatives, 14β-benzoyloxyyohimbine and 14β-p-nitrobenzoyloxyyohimbine

Abstract

Abstract Yohimbine possesses a relatively selective α2-adrenoceptor antagonistic effect and a weak Ca2+ channel blocking activity, so two derivatives, 14β-benzoyloxyyohimbine and 14β-p-nitrobenzoyloxyyohimbine were compared with yohimbine using those parameters. The two derivatives blocked Ca2+-induced contraction of the rat perfused mesenteric vascular bed at 3 times 10−6 M, and developed dose-dependent shifts of the dose-response curve to the right in concentrations from 3 times 10−6 to 10−5M. Yohimbine showed a weak Ca2+ channel-blocking effect only at a concentration of 10−5M. On the other hand, both derivatives at 3 times 10−6 M did not affect the dose-response curve to noradrenaline-induced vasoconstriction. Furthermore, at 10−8 M they had no effect on the dose-response curve to clonidine-induced inhibition of the twitch response of the rat isolated vas deferens evoked by electric stimulation, whereas yohimbine significantly attenuated clonidine-induced inhibition. These results indicate that introduction of bulky substituents into the 14-position of yohimbine intensely potentiated the Ca2+ channel-blocking effects and reduced α-adrenoceptor antagonistic effects compared with those of yohimbine, and suggest that chemical modifications of yohimbine may lead to structurally new types of Ca2+ channel-blockers.