Abstract
We have synthesized the (R)- and (S)-isomers of 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoate (ATPA) by stereochemically certain routes. Our studies in the rat cortical wedge preparation indicate that (R)-ATPA has no observable excitatory effect, while (S)-ATPA has an apparent K(D) of 16 microM. This excitatory response is unaffected by the specific N-methyl-D-aspartate (NMDA) antagonist, D-2-amino-5-phosphonopentanoic acid (DAP5) but is partially blocked by 6-nitro-sulfamoyl[f]quinoxalinedione (NBQX) at concentrations that attenuate the effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA), the effects are however reduced by the nonspecific antagonist kynurenate (KYN), indicating an interaction with a class of kainate receptor.
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