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

Abstract

Aim: To examine whether (-)-stepholidine (SPD) has a direct effect on the Nmethyl-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.

Antagonism of the D2 dopamine receptor enhances tremor but reduces voluntary muscle activation in humans

“…Haloperidol is a known D 2 receptor antagonist, but we must acknowledge that haloperidol can also effect non-dopaminergic neurotransmitter systems (Cobos et al, 2007;Gallagher et al, 1998;Gu et al, 2007;Kroeze et al, 2003;Schotte et al, 1993). However, it has been established that the characteristic extrapyramidal movement effects of haloperidol (and other typical neuroleptics) typically relate to its occupancy of and pharmacological action at the D 2 receptor (Farde et al, 1992;Sykes et al, 2017).…”