Neurochemical studies with the anticonvulsant felbamate in mouse brain.
Felbamate (FBM) is a relatively novel anticonvulsant agent which has been reported to exert its antiepileptic effects by blockade of the glycine recognition site on the N-methyl-D-aspartate subtype of glutamate receptor and potentiation at the gamma-aminobutyric acid (GABA) type A receptor. An increasing number of antiepileptic drugs have, however, additional, neurochemical actions on the GABA and glutamate systems which may contribute to their anticonvulsant activity. As a result, we have investigated the effects of FBM 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 daily for 5 days. Four hours after the final dose, animals were killed and their brains removed for analysis of GABA, glutamate and glutamine concentrations and activities of GABA-transaminase and glutamic acid decarboxylase. Single and repeated doses of FBM were without effect on all of the parameters investigated. These results appear to exclude the possibility that FBM, in addition to its known effects on GABA and glutamate receptors, exerts its antiepileptic effects via an action on the GABA- and glutamate-related neurochemical parameters chosen for investigation.
Fraser
C M
CM
Epilepsy Unit, University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, G11 6NT, Scotland, UK.
Sills
G J
GJ
Forrest
G
G
Thompson
G G
GG
Brodie
M J
MJ
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D000078328:Felbamate; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology*; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D011409:Propylene Glycols; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D000078328:Felbamate