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

Abstract：

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 ([Ca2+]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 micromol/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 Ca2+ 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.

journal_name

Acta Pharmacol Sin

journal_title

Acta pharmacologica Sinica

authors

Gu WH,Yang S,Shi WX,Zhen XC,Jin GZ

doi

10.1111/j.1745-7254.2007.00581.x

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

953-8

issue

7

eissn

1671-4083

issn

1745-7254

journal_volume

28

pub_type

杂志文章

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