1.
Remacemide hydrochloride, a recently developed
antiepileptic drug, is believed to exert its effects, at least in part, via its desglycinyl metabolite,
ARL 12495AA. 2. We have investigated the effects of
ARL 12495AA on several neurochemical parameters in mouse brain. Adult male ICR mice were randomized into two groups and administered
ARL 12495AA (0-75 mg kg-1) intraperitoneally, either as a single dose or once daily for 5 days. 3. Six hours after the final dose, animals were killed and their brains removed. Brain tissues were analysed for concentrations of
gamma-aminobutyric acid (
GABA),
glutamine and
glutamate and for the activities of
GABA-transaminase (
GABA-T) and
glutamic acid decarboxylase (GAD). 4. Single dose
ARL 12495AA was without effect on any of the parameters investigated. 5. Repeated
ARL 12495AA treatment did not alter brain concentrations of
GABA and
glutamine, but at a high dose there was a trend toward reduced brain
glutamate concentrations (P = 0.10). 6. Repeated administration of
ARL 12495AA at a high dose significantly increased
GABA-T activity (P < 0.05) and decreased that of GAD (P < 0.05). 7. These findings may have relevance to the clinical use of
remacemide hydrochloride in human
epilepsy.