Open AccessEffects of (‐)‐stepholidine on NMDA receptors: comparison with haloperidol and clozapine 1
Author(s) -
GU Weihua,
YANG Shen,
SHI Weixing,
ZHEN Xuechu,
JIN Guozhang
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00581.x
Subject(s) - nmda receptor , haloperidol , receptor , chemistry , pharmacology , clozapine , protein subunit , endocrinology , medicine , biochemistry , biology , dopamine , schizophrenia (object oriented programming) , psychiatry , gene
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 NR1a/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 D 1 receptor action underlying an indirect mechanism.