Nicotine induced seizures blocked by mecamylamine and its stereoisomers

Recent genetic research has shown that certain forms of epilepsy may arise from mutations in the genes encoding for the alpha7 and alpha4 neuronal nicotinic acetylcholine receptor (nAChR) ion channels. These receptors are also involved with the induction of nicotine-induced seizures. (+/-)-Mecamylamine (Inversine (R)), a classic nAChR antagonist, potently inhibits nicotine-induced seizures. The purpose of the present study was to assess the inhibitory effects of (+/-)-mecamylamine and its stereoisomers on nicotine-induced seizures in male Sprague-Dawley rats. Rats received saline, ()-mecamylamine, R-(-)-mecamylamine, or S-(+)-mecamylamine (s.c.) at doses of 0.1, 0.3, or 1.0 mg/kg 15 minutes prior to nicotine injection, 3.6 mg/kg (s.c.), an optimal dose for seizure induction. Rats were observed for 30 minutes with seizure latency, duration, and severity as primary measures and locomotor activity recorded as a secondary measure at 5-minute intervals. The results indicate that mecamylamine and each of its stereoisomers block nicotine-induced seizures in a dose-related manner and suggest that the S-(+)- mecamylamine isomer has inhibitory properties more similar to the racemic than to the R-(-)-mecamylamine isomer. The results of this study may be clinically important for the future design of novel anti-seizure medications. (C) 2001 Elsevier Science Inc. All rights reserved.