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

Leach, J. P. , Sills, G. J., Butler, E., Forrest, G., Thompson, G. G. and Brodie, M. J. (1997) Neurochemical actions of the desglycinyl metabolite of remacemide hydrochloride (ARL 12495AA) in mouse brain. British Journal of Pharmacology, 121(5), pp. 923-926. (doi:10.1038/sj.bjp.0701219) (PMID:9222548) (PMCID:PMC1564774)

Leach, J. P. , Sills, G. J., Butler, E., Forrest, G., Thompson, G. G. and Brodie, M. J. (1997) Neurochemical actions of the desglycinyl metabolite of remacemide hydrochloride (ARL 12495AA) in mouse brain. British Journal of Pharmacology, 121(5), pp. 923-926. (doi:10.1038/sj.bjp.0701219) (PMID:9222548) (PMCID:PMC1564774)

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Abstract

Remacemide hydrochloride, a recently developed antiepileptic drug, is believed to exert its effects, at least in part, via its desglycinyl metabolite, ARL 12495AA. 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. Six hours after the final dose, animals were killed and their brains removed. Brain tissues were analysed for concentrations of γ‐aminobutyric acid (GABA), glutamine and glutamate and for the activities of GABA‐transaminase (GABA‐T) and glutamic acid decarboxylase (GAD). Single dose ARL 12495AA was without effect on any of the parameters investigated. 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). 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brodie, Professor Martin and Butler, Mrs Elaine and Leach, Dr John Paul and Forrest, Mr Gerard and Sills, Dr Graeme
Authors: Leach, J. P., Sills, G. J., Butler, E., Forrest, G., Thompson, G. G., and Brodie, M. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:British Journal of Pharmacology
Publisher:Wiley
ISSN:0007-1188
ISSN (Online):1476-5381

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