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

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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.