Anesthetics and Central Cholinergic Function—A Perspective

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Abstract
Current knowledge regarding the role of cholinergic systems in anesthesia is relatively meager. Studies of neurotransmitter function in anesthetic states have focused mainly on the catecholamines and indoleamines. A few early studies indicate that anesthetics generally depress central cholinergic activity in mammals. Moreover, clinical evidence and studies in experimental animals utilizing various cholinergic agonists and antagonists have demonstrated that cholinergic manipulation will affect the anesthetic process. Such information, although fragmentary and sometimes contradictory provided documentation for some definitive participation of ACh [acetylcholine] in the mechanism of anesthesia. Recently several laboratories that are equipped to tackle the methodologic problems have sought to determine the nature and extent of brain ACh metabolic involvement in narcosis, in vivo. The paper by Ngai, Cheney and Finck is the result of one such study. Tracer kinetic analyses of ACh turnover rate in vivo utilizing gas chromatography were employed following rapid inactivation of brain cholinergic enzymatic activity by microwave irradiation. Three types of anesthetics were tested in rats: halothane, enflurane and ketamine. The expected reduction in brain ACh turnover rate was observed after administration of all 3 drugs. The cholinergic system in brain, of course, does not exist as an independent neurochemical entity. The effect of anesthetics in decreasing ACh turnover rate in a particular brain area may conceivably be due to an effect on some other neurotransmitter system in the brain, which in turn induces the depressogenic effect on the particular cholinergic system.