Structure specificities of yohimbine and indoloquinolizidine derivatives in blocking alpha-adrenoceptor and calcium channel

1,12b-Cis-1-p-nitrobenzoyloxyindoloquinolizidine as well as 14 beta-p-nitrobenzoyloxyyohimbine possessed potent calcium channel blocking activities in the isolated rat perfused mesenteric vascular bed. Introduction of the bulky substituents to C-14 of yohimbine or to C-1 of indoloquinolizidine resulted in enhancement of the calcium channel blocking activities. By comparison of chemical structures between yohimbine and indoloquinolizidine, it was found that the E ring of yohimbine had no association with the calcium channel blocking activities. On the other hand, alpha 1- and alpha 2-adrenoceptor antagonistic activities which were tested in the rat mesenteric vascular bed and in the rat vas deferens, respectively, were markedly reduced by such introduction of the bulky substituents to yohimbine and indoloquinolizidine. From these results, it is expected that chemical modifications of indoloquinolizidine at the C-1 position provide new types of agents with calcium channel blocking activities.