Horiuchi H, Yano S, Watanabe K, Yamanaka E, Aimi N, Sakai S
Department of Drug Evaluation and Toxicological Sciences, Chiba University, Japan.
Res Commun Chem Pathol Pharmacol. 1988 Mar;59(3):407-10.
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.
1,12b-顺式-1-对硝基苯甲酰氧基吲哚喹嗪以及14β-对硝基苯甲酰氧基育亨宾在离体大鼠灌注肠系膜血管床中具有强大的钙通道阻滞活性。在育亨宾的C-14位或吲哚喹嗪的C-1位引入庞大取代基会导致钙通道阻滞活性增强。通过比较育亨宾和吲哚喹嗪的化学结构，发现育亨宾的E环与钙通道阻滞活性无关。另一方面，分别在大鼠肠系膜血管床和大鼠输精管中测试的α1和α2肾上腺素能受体拮抗活性，因在育亨宾和吲哚喹嗪上引入此类庞大取代基而显著降低。从这些结果可以预期，在吲哚喹嗪的C-1位进行化学修饰可提供具有钙通道阻滞活性的新型药物。
