Pharmacological characteristics of cyclic homologues of glycine at the N-methyl-D-aspartate receptor-associated glycine site.

In Xenopus oocytes, injected with mRNA from the brain of the rat, the characteristics of the cyclic homologues of glycine, ACPC, ACBC and cycloleucine have been examined. 1-Aminocyclopropane-1-carboxylate was a potent agonist at the NMDA-associated glycine site (EC50 = 0.09 +/- 0.02 microM) and exhibited characteristics consistent with a partial agonist. 1-Aminocyclobutane-1-carboxylate, in addition to its previously described antagonist properties, was found to possess agonist properties of low efficacy. Furthermore, ACBC did not completely block NMDA/glycine-induced currents, which is also consistent with partial agonist characteristics. In addition, small concentrations of glycine (less than 3 microM) did not alter the potency of ACBC, possibly suggesting that it is not simply a competitive glycine antagonist. Cycloleucine was a very weak glycine antagonist. These results suggest that as the size of the ring of cyclic homologues of glycine increases, there is a resulting transition from agonist to mixed agonist/antagonist to antagonist properties.