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        The Use of Ligand Binding in Assays of NMDA Receptor Function

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        The quantification of drug interaction with NMDA receptors has been greatly facilitated by the use of ligand binding assays. The first assays for this receptor measured NMDA-sensitive [3 H]glutamate binding (see 1 for review). However, [3 H]glutamate has relatively low affinity for the receptor, and is also a substrate for transport processes in brain membranes, which can make it difficult to isolate receptor binding from ligand sequestration. The recognition that dissociative anesthetics, such as phencyclidine and ketamine, were NMDA receptor antagonists (2 ,3 ) was an important pharmacological advance, because these drugs were more potent NMDA antagonists that others available at the time. However, phencyclidine also proved to be a difficult ligand to use because of nonspecific binding. The identification of MK801 (dizocilpine) and thienylphencyclidine (TCP) as highly potent and very selective inhibitors of NMDA receptor function (4 6 ) brought the possibility of ligand binding to NMDA receptors into the mainstream.
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