The N-Methyl-D-Aspartate Receptor Complex

AbstractThe effects of agonists of the N-methyl-D-aspartate (NMDA) receptor can be blocked by dissociative anesthetics such as phencyclidine (PCP) in a non-competitive manner. This finding together with the fact that ligand binding to the PCP receptor is dependent on the presence of L-glutamate has led to the suggestion that there may exist an NMDA/PCP receptor complex in mammalian brain tissue. This concept has been extended to the inclusion of a cation channel based on the inhibitory actions of the divalent cation, magnesium. Evaluation of the binding of tritiated TCP (thienylcyclohexylpiperidine) a high affinity ligand for the PCP receptor, under four conditions: in basal, well washed rat cortical membranes; in the presence of L-glutamate; in the presence of magnesium; and in the presence of both magnesium and L-glutamate, with NMDA antagonists and dissociative anesthetics showed that these agents had distinct profiles of activity at the PCP receptor. Furthermore, while both classes of compound could m...