Neurochemical actions of the desglycinyl metabolite of remacemide hydrochloride (ARL 12495AA) in mouse brain

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.