(S)‐homoquisqualate: a potent agonist at the glutamate metabotropic receptor

The synthetic quisqualate analogue, (S)‐homoquisqualate was examined for activity at the glutamate metabotropic receptor, in relation to its ability to stimulate phosphoinositide hydrolysis in rat pup cerebro‐cortical slices. The compound produced a robust increase in hydrolysis (EC50 = 50.2 ± 1.6 μm), which, in common with responses to quisqualate and (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylate ((1S,3R)‐ACPD), was antagonized uncompetitively by l‐2‐amino‐3‐phosphonopropionate (l‐AP3). In contrast to quisqualate which exhibits low efficacy, (S)‐homoquisqualate behaves as a full agonist at the metabotropic receptor.