Anticonvulsant activity of 3,4-dicarboxyphenylglycines in DBA/2 mice.
The 3,4-dicarboxyphenylglycines (3,4-DCPG) inhibit sound-induced seizures in DBA/2 mice with the racemate being notably more potent than either isomer (ED(50) (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 potentiation of anticonvulsant activity between AMPA and mGlu(8) receptors was confirmed by combining (R)-3,4-DCPG with the mGlu(8) agonist (RS)-4-phosphonophenylglycine. This potentiating mechanism provides a novel strategy for the treatment of epileptic seizures.
Moldrich
R X
RX
Department of Pharmacology, Monash University, Melbourne, Victoria, 3800, Australia.
Beart
P M
PM
Jane
D E
DE
Chapman
A G
AG
Meldrum
B S
BS
D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018091:Receptors, AMPA / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013237:Stereoisomerism
C110733:3,4-dicarboxyphenylglycine; D000927:Anticonvulsants; D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8; D005998:Glycine