Pathama Leewanich (1), Michihisa Tohda (1), Kinzo Matsumoto (1), Sanan
Subhadhirasakul (2), Hiromitsu Takayama (3), Norio Aimi (3) and Hiroshi
Watanabe (1,*)
(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