Central cholinergic action produces antagonism to ketamine anesthesia

Ketamine sometimes produces posthypnotic emergency reactions, such as prolonged hallucination or delirium. In a previous paper, we showed that physostigmine, an anticholinesterase agent, counteracts the manifestation of effects of ketamine at some doses. In the present study, we investigated the mechanism of the antagonistic effect of physostigmine on ketamine anesthesia. At first, rats were given ketamine 75 mg/kg. Immediately after the loss of righting reflex, the four groups of rats were given one of the three central cholinergic agents, physostigmine 0.1 mg/kg, oxotremorine 0.05 mg/kg, 4-aminopyridine 3 mg/kg, or saline as the control. The sleeping times were 10.7 +/- 1.0, 12.3 +/- 0.9, 11.4 +/- 1.3 and 21.2 +/- 0.7 min, respectively. The three cholinergic agents antagonized ketamine anesthesia. In the other groups of rats, the central anticholinergic agent, l-hyoscyamine, 0.5 mg/kg, was given subcutaneously for premedication before the above-mentioned procedure. The sleeping times were 16.3 +/- 1.2 min in the physostigmine group, 18.7 +/- 1.0 min in the oxotremorine group and 18.6 +/- 0.8 min in the 4-aminopyridine group. The sleeping time was significantly longer in the premedicated group than in the non-premedicated group, in the case of the three central cholinergic agents. The sleeping time in the saline group, 20.0 +/- 0.4 min, was not significantly different from that of the control in the non-premedicated case. It is, therefore, considered that the central cholinergic action produces antagonism to ketamine anesthesia.