A novel glycine receptor-chloride channel blocker, corymine, from the leaves of Hunteria zeylanica in Thailand

Pathama Leewanich, F. of Medicine, Srinakharinwirot U., Bangkok
Michihisa Tohda, Inst. for Wakan-Yaku, Toyama Medical and Pharmaceutical U., Japan
Kinzo Matsumoto, Inst. for Wakan-Yaku, Toyama Medical and Pharmaceutical U., Japan
Sanan Subhadhirasakul, Assoc. Prof., D. of Pharmacognosy and Pharmaceutical Botany, F. of Pharmaceutical Sci., PSU.
Hiromitsu Takayama, F. of Pharmaceutical Sci., Chiba U., Japan
Norio Aimi, F. of Pharmaceutical Sci., Chiba U., Japan
Hiroshi Watanabe, Inst. for Wakan-Yaku, Toyama Medical and Pharmaceutical U., Japan
Corresponding e-mail : pathama@psm.swu.ac.th

Grant : MONBUSHO
Presented : The 4th NRCT-JSPS Joint Seminar in Pharmaceutical Sciences, "Drug Development through Biopharmaceutical Sciences, November 24-26, 1998, Hat Yai, Songkhla
Key words : Hunteria zeylanica, corymine, glycine receptor-chloride channel blocker

The present study was designed to investigate the pharmacological effects of alkaloidal extrats of Hunteria zeylanica leaves and corymine, a main component. In experimental animals, the crude alkaloidal extracts potentiated the convulsions induced by strychnine (a competitive glycine receptor antagonist) and picrotoxin (a noncompetitive GABAA receptor antagonist) and prolonged pento-barbital-induced sleeping time. Corymine potentiated the convulsions induced by strychnine and picrotoxin, but had no effect on the sleeping time. In electrophysiological studies, corymine partially reduced GABA current, whereas marked reductions were observed in glycine current in a noncompetitive fashion. This alkaloid, however, had no effect on acetylcholine- and serotonin-induced currents. Corymine decreased the ED50 of strychnine but not that of DIDS (a chloride channel blocker). The desensitization phase of glycine current showed two exponentials and corymine preferentially sup-pressed the fast component. In contrast, strychnine affected both of them the same extent, and DIDS preferentially inhibited the slow component. When corymine, strychnine or DIDS was applied re-peatedly, the corymine- and strychnine-induced inhibitions were not use-dependent, while DIDS inhibition was use-dependent. These studies suggest that corymine is a glycine receptor-chloride channel blocker that its mechanism of action is different from that of DIDS.
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