Abstract
( super(3)H)dextrorphan recognition sites were characterized in rat brain membranes. The pharmacological profile and regional distribution of ( super(3)H)dextrorphan binding sites appear to distinguish these sites from those labeled either by ( super(3)H)dextromethorphan or by putative sigma receptor radioligands. Data from thoroughly washed forebrain membranes suggest that ( super(3)H)dextrorphan predominantly labels a high affinity site defined by the activated state of the N-methyl-D-aspartate (NMDA) receptor-channel complex. Regulation of ( super(3)H)dextrorphan binding by specific modulators of NMDA receptor function suggests that ( super(3)H)dextrorphan binding is predominantly localized to a domain of the receptor-channel complex also recognized by the prototypical noncompetitive antagonist radioligands (+)-( super(3)H)5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-i mine (MK-801) and ( super(3)H)1-(1-(2-thienyl)cyclohexyl)-piperidine (TCP). The critical relationship between ( super(3)H)dextrorphan binding and activation of the NMDA receptor-complex is suggested by the profound dependence of ( super(3)H)dextrorphan binding on glutamate in well washed membranes.