Interactions of cholinesterase inhibitors and glucocorticoids with ketamine and pentobarbitone-induced general anaesthesia in the rat: possible effects on central cholinergic activity.

Doses of 100, 150 and 200 micrograms kg-1 of the cholinesterase inhibitor neostigmine reverse the anaesthetic action of ketamine. The antagonistic effect is increased as the dose is increased. The duration of anaesthesia induced by pentobarbitone is reversed by the cholinesterase inhibitor in doses of 150, 200 and 250 micrograms kg-1. Choline, in a dose of 50 mg kg-1, significantly antagonizes the action of the two anaesthetics, whereas hemicholinium-3, an inhibitor of the uptake of choline and the synthesis of acetylcholine, markedly potentiates their action. Dexamethasone induces a significant reduction of the duration of anaesthesia produced by ketamine and pentobarbitone. The potentiation of the anaesthetic effect caused by hemicholinium-3 is also reversed by dexamethasone. The acetylcholine content in rat cerebral cortex is increased after treatment with ketamine and pentobarbitone. Measurements of the course of the plasma level of pentobarbitone do not reveal alterations in the pharmacokinetic profile by either neostigmine or dexamethasone. These results indicate that central cholinergic systems may somehow be involved in the anaesthesia induced by ketamine and pentobarbitone and that the interactions described in this paper may be the result of modification by neostigmine and dexamethasone of the alterations in cholinergic activity caused by the two anaesthetics.