文摘
Replacement of the methyl group of the AMPA receptor agonist 2-amino-3-[3-hydroxy-5-(2-methyl-2H-5-tetrazolyl)-4-isoxazolyl]propionic acid (2-Me-Tet-AMPA) with a benzyl group provided the first AMPAreceptor agonist, compound 7, capable of discriminating GluR2-4 from GluR1 by its more than 10-foldpreference for the former receptor subtypes. An X-ray crystallographic analysis of this new analogue incomplex with the GluR2-S1S2J construct shows that accommodation of the benzyl group creates a previouslyunobserved pocket in the receptor, which may explain the remarkable pharmacological profile of compound7.