Noncompetitive excitatory amino acid receptor antagonists

Divalent cations, phencyclidine-like drugs, glycine analogues and polyamines all modulate NMDA receptors whereas barbiturates and some arthropod toxins reduce channel responses to non-NMDA receptor agonists.

Abstract

In the first article in this series, Watkins, Krogsgaard-Larsen and Honoré outlined the structure-activity requirements at the receptor sites for excitatory amino acids in the mammalian CNS. The postsynaptic depolarizing actions of glutamate are thought to be mediated by NMDA, AMPA and kainate receptors. Here David Lodge and Kenneth M. Johnson review some of the recent developments in the pharmacology of other means by which the function of these receptors may be modulated. Divalent cations, phencyclidine-like drugs, glycine analogues and polyamines all modulate NMDA receptors whereas barbiturates and some arthropod toxins reduce channel responses to non-NMDA receptor agonists. Modes of action and implications for physiology and pathophysiology are discussed.