title: Ca2+ channel-blocking effect of the yohimbine derivatives, 14 beta-benzoyloxyyohimbine and 14 beta-pho-nitrobenzoyloxyyohimbine.
abstract: Yohimbine possesses a relatively selective alpha 2-adrenoceptor antagonistic effect and a weak Ca2+ channel blocking activity, so two derivatives, 14 beta-benzoyloxyyohimbine and 14 beta-rho-nitrobenzoyloxyyohimbine were compared with yohimbine using those parameters. The two derivatives blocked Ca2+-induced contraction of the rat perfused mesenteric vascular bed at 3 X 10(-6) M, and developed dose-dependent shifts of the dose-response curve to the right in concentrations from 3 X 10(-6) to 10(-5) M. Yohimbine showed a weak Ca2+ channel-blocking effect only at a concentration of 10(-5) M. On the other hand, both derivatives at 3 X 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 alpha-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.
mesh_terms: D000317:Adrenergic alpha-Antagonists; D000818:Animals; D002121:Calcium Channel Blockers; D002122:Calcium Chloride / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; C053208:14-(4-nitrobenzoyloxy)yohimbine; D015016:Yohimbine; C053209:14-benzoyloxyyohimbine; D002122:Calcium Chloride; D003000:Clonidine; D009638:Norepinephrine