Levamisole-induced reduction in seizure threshold: a possible role of nicotinic acetylcholine receptor-mediated pathway.
Levamisole produces seizures in man and is also known to activate the neuronal nicotinic acetylcholine receptors, which are further known to elicit seizure activity. Therefore, the present study has been designed to investigate the role of nicotinic acetylcholine receptor activation in the seizure-inducing effect of levamisole. Levamisole, at the doses of 5, 10 and 20 mg kg(-1), i.p. were used to elicit seizures in mice. Seizures were assessed in terms of the onset time of Straub's tail phenomenon, jerky movements of whole body and convulsions. Additionally, an isobolographic design was used to examine the interaction of systemically administered levamisole and nicotine. Prior administration of 2, 2, 6, 6-tetramethylpiperidin-4-yl heptanoate (TMPH), a selective inhibitor of neuronal nicotinic acetylcholine receptors, markedly attenuated the seizure-inducing effect of levamisole. Moreover, administration of TMPH per se did not produce any behavioural changes in mice. Furthermore, nicotine was observed exert a synergistic interaction with levamisole. Therefore, it may be suggested that levamisole-induced reduction in seizure threshold might be ascribed to the activation of a neuronal nicotinic acetylcholine receptor activation-linked mechanism.
Rehni
Ashish K
AK
Chitkara College of Pharmacy, Chandigarh-Patiala National Highway, Patiala, Punjab, India. ashishkrehni@gmail.com
Singh
Thakur Gurjeet
TG
D000818:Animals; D000969:Antinematodal Agents / Q000008:administration & dosage / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007978:Levamisole / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000633:toxicity*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced*
D000969:Antinematodal Agents; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D007978:Levamisole; D009538:Nicotine