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 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 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.
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Projects supported by the Ministry of Science and Technology (No 973-2003CB51 54000) and the National Natural Science Foundation of China (No 30230130 and 30572168).
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Gu, Wh., Yang, S., Shi, Wx. et al. Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine. Acta Pharmacol Sin 28, 953–958 (2007). https://doi.org/10.1111/j.1745-7254.2007.00581.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00581.x