Effects of physostigmine, scopolamine, and mecamylamine on the sleeping time induced by ketamine in the rat.

Male Sprague-Dawley rats weighing 116--241 g were injected i.p. with ketamine hydrochloride, 80 mg per kilo of body weight. Immediately after loss of righting reflex, scopolamine, physostigmine, and mecamylamine were administered i.p. to different groups of rats. Control animals received sterile saline by the same route. The ketamine-induced sleeping time was significantly prolonged by physostigmine and scopolamine, but not by mecamylamine. After the delayed injection of physostigmine, the ketamine sleeping time was longer. These results, although too preliminary for a mechanistic interpretation, suggest that multiple neurotransmitter systems, probably including the cholinergic system, are involved in the mechanism of action of ketamine-induced narcosis.