Effects of (-)-stepholidine on NMDA receptors:comparison with haloperidol and clozapine  

作　　者：Wei-hua GU Shen YANG Wei-xing SHI Xue-chu ZHEN Guo-zhang JIN 

机构地区：[1]Department of Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes of Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, China [2]Neuropsychopharmacological Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, USA

出　　处：《Acta Pharmacologica Sinica》2007年第7期953-958,共6页中国药理学报（英文版）

基　　金：Projects supported by the Ministry of Science and Technology(№ 973-2003CB5154000);the National Natural Science Foundation of China(№ 30230130 and 30572168)

摘　　要：Aim： To examine whether （-）-stepholidine （SPD） has a direct effect on the N- methyl-D-aspartic acid receptors （NMDAR） containing the NMDA receptor subunits NR2A or NR2B and to compare its effect with those of haloperidol （Hal） and clozapine （Cloz）. Methods： NMDAR was transiently expressed in human embryonic kidney 293 （HEK293） cells. Changes in intracellular calcium concentration （[Ca^2＋]i） induced by NMDAR activation were monitored with Fura-2 ratio imaging techniques. Results： SPD had no significant effects on either subunit of NMDAR at a concentration of less than 100 μmol/L. Hal selectively inhibited NMDAR containing the NR2B subunit, whereas Cloz inhibited both subunits of NMDAR. Although both Hal and Cloz inhibited NRI a/NR2B receptor-mediated Ca^2＋ influx, their effects were different. Hal was more potent and had a faster peak effect than Cloz. Conclusion： Both Hal and Cloz inhibit NMDAR-mediated function, whereas SPD produced only a little inhibition at a high concentration. Based on our other studies, the modulation of SPD on NMDAR function may be via D1 receptor action underlying an indirect mechanism.Aim： To examine whether （-）-stepholidine （SPD） has a direct effect on the N- methyl-D-aspartic acid receptors （NMDAR） containing the NMDA receptor subunits NR2A or NR2B and to compare its effect with those of haloperidol （Hal） and clozapine （Cloz）. Methods： NMDAR was transiently expressed in human embryonic kidney 293 （HEK293） cells. Changes in intracellular calcium concentration （[Ca^2＋]i） induced by NMDAR activation were monitored with Fura-2 ratio imaging techniques. Results： SPD had no significant effects on either subunit of NMDAR at a concentration of less than 100 μmol/L. Hal selectively inhibited NMDAR containing the NR2B subunit, whereas Cloz inhibited both subunits of NMDAR. Although both Hal and Cloz inhibited NRI a/NR2B receptor-mediated Ca^2＋ influx, their effects were different. Hal was more potent and had a faster peak effect than Cloz. Conclusion： Both Hal and Cloz inhibit NMDAR-mediated function, whereas SPD produced only a little inhibition at a high concentration. Based on our other studies, the modulation of SPD on NMDAR function may be via D1 receptor action underlying an indirect mechanism.

关 键 词：（-）-stepholidine HALOPERIDOL CLOZAPINE NMDA receptor calcium imaging neuro-leptics 

分 类 号：R971.3[医药卫生—药品]