Inhibitory effects of corymine-related compounds on glycine receptors expressed in Xenopus oocytes.
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.
Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Sugitani, Japan.
P
P
Leewanich
M
M
Tohda
K
K
Matsumoto
S
S
Subhadhirasakul
H
H
Takayama
N
N
Aimi
H
H
Watanabe
D000470:Alkaloids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D003292:Convulsants / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000235:genetics; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects / Q000235:genetics; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors* / Q000235:genetics; D013329:Structure-Activity Relationship; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology
D000470:Alkaloids; D003292:Convulsants; D018079:Receptors, GABA; D018009:Receptors, Glycine; C114764:deformylcorymine; C114765:pleiocarpamine; D005680:gamma-Aminobutyric Acid; C108901:corymine; D005998:Glycine