This chapter discusses the allosteric modulation of N–methyl-D-aspartute (NMDA) receptors. It focuses on the NMDA-preferring glutamate receptor. NMDA receptors are involved in a wide range of physiological and pathophysiological events, and this has resulted in a great deal of interest in the development of tools to probe and manipulate NMDA receptor function. Moreover, many studies have demonstrated that the activity of the NMDA receptor can be modulated by a wide range of endogenous agents. The purpose of this chapter, therefore, is to examine the actions of the known modulators of the receptor in terms of their binding sites, and to try to determine how these binding sites interact with each other. By understanding the interactions between the known modulators of this receptor it may be possible to comprehend better how the receptor may operate in different circumstances, and it may also be possible to target more accurately therapeutic agents to interrupt specific NMDA receptor-mediated events.
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