PMID: 8967976Dec 1, 1996Paper

Subtype-selective inhibition of N-methyl-D-aspartate receptors by haloperidol

Molecular Pharmacology
V I IlyinR M Woodward

Abstract

Previous studies indicate that haloperidol, a therapeutically useful antipsychotic drug, inhibits neuronal N-methyl-D-aspartate (NMDA) responses and has neuroprotective effects against NMDA-induced brain injury. To further characterize this inhibition, we used electrical recordings to assay the effects of haloperidol on four diheteromeric subunit combinations of cloned rat NMDA receptors expressed in Xenopus laevis oocytes: NR1A coexpressed with NR2A, NR2B, NR2C, or NR2D. Haloperidol selectively blocks NR1A/2B subunit combinations (IC50 = approximately 3 microM; maximum inhibition, approximately 85%), whereas the other subunit combinations are > or = 100-fold less sensitive (IC50 = >300 microM). Inhibition of NR1A/2B receptors is insurmountable with respect to glutamate and glycine and does not exhibit voltage dependence. The splice variant combinations NR1B/2B and NR1e/2B are also blocked by haloperidol. In oocytes from some frogs, 30-100 microM haloperidol induces potentiation of NR1A/2A receptor responses. NMDA responses in E16-17 rat cortical neurons cultured for < or = 10 days are inhibited by haloperidol at the same potency and to the extent as NR1/2B receptors (IC50 = approximately 2 microM; maximum inhibition, approxima...Continue Reading

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