Na+ channel effects of remacemide and desglycinyl-remacemide in rat cortical synaptosomes

Santangeli, S., Sills, G. J., Thompson, G. G. and Brodie, M. J. (2002) Na+ channel effects of remacemide and desglycinyl-remacemide in rat cortical synaptosomes. European Journal of Pharmacology, 438(1-2), pp. 63-68. (doi: 10.1016/S0014-2999(02)01297-9) (PMID:11906711)

Abstract

The effects of the novel anticonvulsant, remacemide hydrochloride and its active metabolite, desglycinyl-remacemide, on veratridine-induced Na+ influx in rat cortical synaptosomes were investigated and compared to established Na+ channel blocking antiepileptic drugs. Remacemide and desglycinyl-remacemide reduced veratridine-stimulated Na+ influx to 30.7% (IC50=160.6 μM) and 13.2% (IC50=85.1 μM) of control, respectively. Carbamazepine, phenytoin and lamotrigine similarly reduced Na+ influx to 20.1% (IC50=325.9 μM), 79.8% and 27.9% (IC50=23.0 μM) of control, respectively. Resting internal Na+ concentrations were significantly increased by desglycinyl-remacemide (1 and 10 μM) and, conversely, decreased by desglycinyl-remacemide and carbamazepine (both 1000 μM). These studies support previous electrophysiological investigations, which suggest that remacemide and desglycinyl-remacemide exert their antiepileptic effects, at least in part, by an inhibitory action on voltage-gated Na+ channels. Desglycinyl-remacemide may have an additional action on Na+ homeostasis that merits further exploration.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Brodie, Professor Martin and Sills, Dr Graeme
• Authors: Santangeli, S., Sills, G. J., Thompson, G. G., and Brodie, M. J.
• College/School: 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: European Journal of Pharmacology
• Publisher: Elsevier
• ISSN: 0014-2999
• ISSN (Online): 1879-0712