An AChE inhibitor
Edrophonium is a competitive inhibitor of acetylcholinesterase (AChE) [1]. AChE is an extrinsic membrane-hound enzyme that functions in the central and peripheral nervous systems. AChE rapidly terminates the ACh receptor-mediated signal transmission by hydrolyzing Ach. Inhibition of AChE results in accumulation of ACh in the synaptic cleft and leads to impeded neurotransmission [2].
In vitro: Edrophonium inhibited AChE activity in human red blood cells, purified calf forebrain, and octopus brain with Ki values of 0.2, 0.2, and 0.4 μM, respectively. The IC50s were 0.2, 0.05, and 0.5 μM, respectively [1].
In vivo: In symptomatic patients without coronary artery disease, edrophonium (80 μg/kg, intravenous bolus) induced chest pain [3]. Edrophonium increased esophageal amplitude and repetitive contractions. Edrophonium was useful for provoking esophageal chest pain [3]. In infants and children during N2O-halothane anesthesia, the ED50 for edrophonium is 128 μg/kg for adults [4]. In patients anaesthetized with nitrous oxide and halothane undergoing kidney transplant nephrectomy or transplantation of a live related donor kidney, patients undergoing transplant nephrectomy showed a significant increase in elimination half-life and a significant decrease (67%) in serum clearance when compared with kidney transplant recipients or patients with normal renal function [5].
参考文献:
[1] Boyle N A J, Talesa V, Giovannini E, et al.? Synthesis and study of thiocarbonate derivatives of choline as potential inhibitors of acetylcholinesterase[J]. Journal of medicinal chemistry, 1997, 40(19): 3009-3013.
[2] Quinn D M.? Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transition states[J]. Chemical Reviews, 1987, 87(5): 955-979.
[3] Cronnelly R, Morris R B, Miller R D.? Edrophonium: duration of action and atropine requirement in humans during halothane anesthesia[J]. Anesthesiology, 1982, 57(4): 261-266.
[4] Fisher D M, Cronnelly R, Sharma M, et al.? Clinical pharmacology of edrophonium in infants and children[J]. Anesthesiology, 1984, 61(4): 428-433.
[5] Morris R B, Cronnelly R, Miller R D, et al.? Pharmacokinetics of edrophonium in anephric and renal transplant patients[J]. British journal of anaesthesia, 1981, 53(12): 1311-1314.
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