Anticonvulsant activity of 3,4-dicarboxyphenylglycines in DBA/2 mice

The 3,4-dicarboxyphenylglycines (3,4-DCPG) inhibit sound-induced seizures i n DBA/2 mice with the racemate being notably more potent than either isomer (ED50 (nmol, i.c.v.)): (RS)-3,4-DCPG (0.004; 86 mg/kg, i.p.)>>the mGlu(8) agonist (S)-3,4-DCPG (0.11)>the AMPA antagonist (R)-3,4-DCPG (0.38). A pote ntiation of anticonvulsant activity between AMPA and mGlu(8) receptors was confirmed by combining (R)-3,4-DCPG with the mGlu(8) agonist (RS)-4-phospho nophenylglycine. This potentiating mechanism provides a novel strategy for the treatment of epileptic seizures. (C) 2001 Elsevier Science Ltd. All rig hts reserved.