NEW DEVELOPMENTS IN THE MOLECULAR PHARMACOLOGY OF ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONATE AND KAINATE RECEPTORS

Separation of non-N-methyl-D-aspartate subtypes of glutamate receptors , known as alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA ) and kainate receptors, is traced through conventional pharmacology t o molecular biology. The physiology and pharmacology of recombinant re ceptor subtypes (GluR1-7 and KA1-2) are described Competitive antagoni sts, e.g., the quinoxalinedione, dihydroxy-6-nitro-7-sulphamoyl-benz(F )quinoxaline, and the decahydroisoquinoline, 3S,4aR,6R,8aR-6-[2-(1(2)H -tetrazol-5-yl) ethyl]-decahydroisoquinoline-3-carboxylate, have a bro ad antagonist spectrum, except that the latter is inactive on GluR6. T he 2,3-benzodiazepines noncompetitively antagonise the AMPA receptor G luR1-4, Desensitisation of AMPA (GluR1-4) and kainate (GluR5-7 and KA1 -2) receptors is blocked by cyclothiazide and concanavalin A, respecti vely, Polyamine toxins block AMPA receptors not containing GluR2 and u nedited kainate receptors (GluR5-6). These data correlate well with re sults on native neurons characterised by techniques such as in situ hy bridisation.