可立米宁相关化合物对非洲爪蟾卵母细胞中表达的甘氨酸受体的抑制作用。

Inhibitory effects of corymine-related compounds on glycine receptors expressed in Xenopus oocytes.

作者信息

Leewanich P, Tohda M, Matsumoto K, Subhadhirasakul S, Takayama H, Aimi N, Watanabe H

机构信息

Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Sugitani, Japan.

出版信息

Jpn J Pharmacol. 1998 Jun;77(2):169-72. doi: 10.1254/jjp.77.169.

DOI:10.1254/jjp.77.169

PMID:9681574

Abstract

We examined the effects of 4 corymine-related compounds on glycine-induced chloride current in Xenopus oocytes. Dihydrocorymine, N-demethyl-3-epi-dihydrocorymine and deformylcorymine dose-dependently decreased the glycine current with IC50 values of 34, 37 and 55 microM, respectively. The effect of these compounds on the glycine current was more potent than that of pleiocarpamine (IC50 > 1 mM). N-demethyl-3-epi-dihydrocorymine and dihydrocorymine, at 100 microM, also decreased the gamma-aminobutyric acid-induced current by 65% and 22%, respectively, whereas deformylcorymine and pleiocarpamine failed. The inhibitory action of deformylcorymine on the glycine current was noncompetitive. These results suggest that deformylcorymine is a novel specific noncompetitive glycine receptor antagonist. The structure-activity relationship of these compounds was discussed.

摘要

我们研究了4种与紫堇明相关的化合物对非洲爪蟾卵母细胞中甘氨酸诱导的氯离子电流的影响。二氢紫堇明、N-去甲基-3-表二氢紫堇明和去甲酰基紫堇明剂量依赖性地降低了甘氨酸电流，其IC50值分别为34、37和55微摩尔。这些化合物对甘氨酸电流的作用比多果夹胺（IC50>1毫摩尔）更强。100微摩尔的N-去甲基-3-表二氢紫堇明和二氢紫堇明也分别使γ-氨基丁酸诱导的电流降低了65%和22%，而去甲酰基紫堇明和多果夹胺则无此作用.去甲酰基紫堇明对甘氨酸电流的抑制作用是非竞争性的。这些结果表明去甲酰基紫堇明是一种新型的特异性非竞争性甘氨酸受体拮抗剂。讨论了这些化合物的构效关系。