Haloperidol interacts with the strychnine-insensitive glycine site at the NMDA receptor in cultured mouse hippocampal neurones.
N-Methyl-D-aspartate (NMDA)-evoked responses in voltage-clamped hippocampal neurones in culture were reversibly, but not completely, attenuated on superfusion with micromolar concentrations (0.1-100 microM) of haloperidol with an IC50 (+/- S.E.M.) value of 1.9 +/- 0.2 microM (n = 7). In contrast, kainate- and (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-evoked responses were relatively unaffected on application of 50 microM haloperidol. The NMDA receptor antagonist action of haloperidol was neither competitive in nature nor voltage-dependent but was reduced upon elevation of the extracellular concentration of glycine. Furthermore, in the absence of added glycine haloperidol (at 0.1 microM) frequently potentiated NMDA-evoked responses. Haloperidol thus appears to be a partial agonist for the strychnine-insensitive glycine site associated with the NMDA receptor-channel complex.
Fletcher
E J
EJ
Department of Physiology, University of Toronto, ONT, Canada.
MacDonald
J F
JF
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013331:Strychnine / Q000494:pharmacology
D016194:Receptors, N-Methyl-D-Aspartate; D013331:Strychnine; D006220:Haloperidol; D005998:Glycine