Mediation of nicotine-induced convulsions by central nicotinic receptors of the 'C6' type.
The nature of the central receptors mediating the convulsant actions of nicotine has been investigated. Clonic tonic convulsions were seen in mice following intracerebroventricular (i.c.v.) injection of nicotinic agonists. (-)Nicotine was the most potent agonist tested, with a CD50 of 7.9 X 10(-9) mol. (+)Nicotine, cytisine, DMPP and lobeline were 10-100 times less potent than (-)nicotine. Nicotine induced convulsions were antagonized by ganglion blocking drugs administered intraventricularly. Pentolinium was the most potent antagonist, with an ED50 of 4 X 10(-11) mol. The ganglion-blockers also produced convulsions in their own right at doses 80-1000 times the anti-nicotine ED50 dose. 'C10' blockers, such as d-tubocurarine, did not antagonize nicotine-convulsions, but produced convulsions in their own right. alpha-Bungarotoxin had neither convulsant nor anticonvulsant activity at the doses tested. It is concluded that the central receptors mediating this nicotinic effect resemble ganglionic ('C6') receptors, rather than neuromuscular ('C10') receptors.
D000818:Animals; D004357:Drug Synergism; D005731:Ganglionic Stimulants / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology
D005731:Ganglionic Stimulants; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D009538:Nicotine