Pathama Leewanich (1), Michihisa Tohda (1), Kinzo Matsumoto (1), Sanan
Subhadhirasakul (2), Hiromitsu Takayama (3), Norio Aimi (3) and Hiroshi
(1) Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
(2) Department of Pharmaceutical Botany and Pharmacognosy, Faculty of Pharmaceutical Sciences, Prince of Songkhla University, Hat-yai Songkhla 90112, Thailand
(3) Faculty of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan
(*) To whom correspondence should be addressed.
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.
Keywords: Glycine current, gamma-Aminobutyric acid current, Corymine-related compound