Neurochemical studies with the anticonvulsant felbamate in mouse brain

Felbamate (FBM) is a relatively novel anticonvulsant agent which has been r eported to exert its antiepileptic effects by blockade of the glycine recog nition site on the N-methyl-D-aspartate subtype of glutamate receptor and p otentiation at the gamma-aminobutyric acid (GABA) type A receptor. An incre asing number of antiepileptic drugs have, however, additional, neurochemica l actions on the GABA and glutamate systems which may contribute to their a nticonvulsant activity. As a result, we have investigated the effects of FB M on several GABA- and glutamate-related neurochemical parameters in mouse brain. Adult male ICR mice were randomised into two groups and administered FBM (0-100 mg kg(-1)) intraperitoneally either as a single dose or twice d aily for 5 days. Four hours after the final dose, animals were killed and t heir brains removed for analysis of GABA, glutamate and glutamine concentra tions and activities of GABA-transaminase and glutamic acid decarboxylase. Single and repeated doses of FBM were without effect on all of the paramete rs investigated. These results appear to exclude the possibility that FBM, in addition to its known effects on GABA and glutamate receptors, exerts it s antiepileptic effects via an action on the GABA- and glutamate-related ne urochemical parameters chosen for investigation. (C) 1999 Academic Press.