THE EFFECT IN VITRO OF VOLATILE ANESTHETICS ON THE ACTIVITY OF CHOLINESTERASES¹

Abstract

Because the mechanism of anesthesia is unknown, the relationship between anesthetics and enzymes essential to brain function may be an important one. Therefore, the effect of 8 volatile anesthetics on the enzymatic activity of solubilized, purified dog brain and human erythrocyte acetylcholinesterase (AChE) and human serum cholinesterase (ChE) was studied in vitro. Serum ChE was found to be insensitive to saturated solutions of all the anesthetics studied. However, brain and erythrocyte AChE were reversibly inhibited in a dose-dependent manner by all 8 anesthetics in concentrations exceeding those used in clinical practice. Kinetic analysis revealed a mixed (competitive, non-competitive) type of inhibition with the exception of the ether-erythrocyte AChE interaction which was characterized by competitive inhibition. Ether and methoxyflurane were found to depress the AChE activity the most and isoflurane and enflurane the least. The concentrations of anesthetic in the gas .phase necessary for 50% inhibition of erythrocyte AChE activity (Iso) were calculated for 5 anesthetics and found to correlate with their water-gas partition coefficients. These data suggest that the effect in uitro of volatile anesthetics on the catalytic activity of cholinesterases is a variable one and may be unrelated to anesthetic potency in vim. The implications of these data concerning anesthetic-active site interactions are discussed.

Does Xenon Anesthesia Inhibit Cholinesterases?

“…Although we postulated that the cholinergic effects of xenon anesthesia might be due to the inhibition of cholinesterases, as shown with ether and cyclopropane in the 1970s, 4,5 our data demonstrate that xenon has no significant effect on cholinesterases in vitro. Thus, we believe that the cholinergic effects or increased acetylcholine concentration in the brain resulting from the administration of xenon are due to an increased release of acetylcholine from the cholinergic nervous system.…”

“…1,2 A microdialysis technique showed transient increases in acetylcholine concentration in rat cerebral cortex when xenon was inhaled as an anesthetic, 3 while ether and cyclopropane have been known to inhibit acetylcholinesterase at clinically relevant concentrations. 4,5 Therefore, we hypothesize that xenon may affect the cholinergic nervous system by inhibiting acetylcholinesterase.…”

Neurotransmitter Metabolizing Enzymes and Plasma Butyrylcholinesterase in Mice Exposed to Trichloroethylene

“…(Adamson 1977;Benton et al 1975). TCE at high concentrations (1%) is known to inhibit purified brain AChE in vitro (Braswell & Kitz 1977). Such concentrations may be reached during anaesthesia but the concentration used in this study, 170 p.p.m., had no effect on brain AChE in vitro.…”

Swine models in the design of more effective medical countermeasures against organophosphorus poisoning

“…Serum ChE activity (butyrylcholinesterase, BuChE) can be inhibited by several drugs, including anaesthetics. Some halogenated compounds such as enflurane, halothane or isoflurane induce inhibition in the range of 10-20% (Braswell and Kitz, 1977;Kaniaris et al, 1978;Choudhury et al, 1989). In a series of experiments performed at DRDC Suffield (unpublished results), we also found similar inhibition of ChE activity.…”