Excitatory amino acid receptors: Multiplicity and ligand specificity of the NMDA and AMPA receptor subtypes

Abstract

Central excitatory amino acid (EAA) receptors are most conveniently subdivided into five main classes, most of which, if not all, are heterogeneous: NMDA, AMPA, kainic acid (KAIN), metabotropic, and L-AP4 receptors. The AMPA and KAIN receptors have very similar pharmacology in vivo , and these receptors are often collectively named non-NMDA EAA receptors. The Amanita muscaria constituent, ibotenic acid, which is an analogue of glutamic acid, interacts more or less effectively with all subtypes of EAA receptors. Ibotenic acid has, however, been used as a lead structure for the development of a number of specific ligands for NMDA and AMPA receptors. Thus, the aspartic acid analogue of ibotenic acid, AMAA, is a specific NMDA agonist. Whereas AMPA and 4-AHCP are specific agonists at AMPA receptors, APPA is a partial AMPA agonist, and AMOA is an antagonist at non-NMDA EAA receptors.