依托咪酯类似物可减轻大鼠肾上腺皮质功能的抑制，稳定血液动力学，提高行为学的恢复
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An Etomidate Analogue With Less Adrenocortical Suppression,Stable Hemodynamics, and Improved Behavioral Recovery in Rats
背景与目的
ET-26盐酸盐（ET-26HCl）是一种新型的依托咪酯类似物，其可减轻依托咪酯引起的肾上腺皮质功能抑制，同时具有依托咪酯的快速起效镇静催眠和稳定的血流动力学特征。本研究比较了大鼠使用ET-26HCl，依托咪酯和镇静催眠药物异丙酚的麻醉效果，血流动力学稳定性以及恢复情况。
方 法
运用高效液相色谱法测定了3只大鼠的血浆和肝脏匀浆样品中ET-26HCl的代谢半衰期。ET-26HCl，依托咪酯和异丙酚的半数有效剂量（HD50）是通过上下法来确定的。静脉注射等剂量的异丙酚，依托咪酯，ET-26HCl来评估麻醉效果和平均动脉压。采用酶联免疫法分析皮质酮的浓度。使用等效剂量的异丙酚，依托咪酯，ET-26HCl和生理盐水进行Morris水迷宫测试，对大鼠从镇静催眠状态到清醒进行了评估。
结 果
大鼠血浆ET-26HCl的代谢半衰期为81±6分钟，肝脏匀浆样品为126±12分钟。体内实验显示，ET-26HCl引起翻正反射消失比依托咪酯低3倍。 在等剂量下，和ET-26HCl（-10.7 mm Hg）和依托咪酯（-19.4 mm Hg）相比，异丙酚致平均动脉压降低更显著。当用促肾上腺皮质激素（ACTH1-24）刺激后，15、30和60分钟，ET-26HCl组血清皮质酮水平显著高于依托咪酯组。 ET-26HCl静脉注射麻醉引起的空间定向恢复较异丙酚更快，但自发活动恢复较慢。
结 论
ET-26HCl具有类似于依托咪酯的麻醉强度和血液动力学稳定性，但是它较依托咪酯更少引起肾上腺皮质功能抑制。其与依托咪酯类似，ET-26HCl静脉注射麻醉引起的空间定向恢复较异丙酚更快。
原始文献摘要
Bin Wang,Jun Yang，Jun Chen,et al.An Etomidate Analogue With Less Adrenocortical Suppression,Stable Hemodynamics,and Improved Behavioral Recovery in Rats.Anesth Analg.2017 Aug;125(2):442-450. doi: 10.1213/ANE.0000000000002063
BACKGROUND: ET-26 hydrochloride (ET-26HCl) is a novel etomidate analogue designed to alleviate the adrenocortical suppression caused by etomidate while retaining the rapid sedative-hypnotic onset and stable hemodynamic features of etomidate. This study compared the anesthetic effect, hemodynamic stability, and recovery profiles of ET-26HCl, etomidate, and the sedative-hypnotic drug propofol in rats.
METHODS: The metabolic half-life of ET-26HCl was determined in vitro using high performance liquid chromatography analysis of samples of rat plasma and liver homogenates taken from 3 animals.Hypnotic median effective doses (HD50) of ET-26HCl,etomidate,and propofol were determined by upand-down methods. Anesthesia effect and mean arterial pressure were estimated using equivalent intravenous (IV) doses of propofol,etomidate, and ET-26HCl in the rats.Serum concentrations of corticosterone were analyzed by enzyme-linked immunosorbent assay.The ability of rats to from the sedative-hypnotic effects of the drugs was evaluated using open field and Morris water maze tests at equipotent doses of propofol, etomidate,ET-26HCl,and normal saline.
RESULTS: The metabolic half-life of ET-26HCl was 81 ± 6 minutes in rat plasma and 126 ± 12 minutes in incubation liver homogenate (mean ± standard deviation), respectively.In vivo experiments showed that the potency of ET-26HCl to cause a loss of righting reflex in rats was 3 times lower than that of etomidate in the rats. IV propofol caused a greater decrease in mean arterial pressure relative to the baseline (−27.9 mm Hg) than did ET-26HCl(−10.7 mm Hg) and etomidate (−19.4 mm Hg)at equipotent doses. Serum corticosterone levels after drug administration were significantly higher in the ET-26HCl group than in the etomidate group at equivalent doses when measured 15 (P <.001),30 (P <.001), and 60 (P = .002) minutes after stimulation with adrenocorticotropic hormone(ACTH1–24). Recovery of spatial orientation from anesthesia induced by an IV bolus injection was faster with ET-26HCl than with propofol, but recovery of spontaneous activity was slower.
CONCLUSIONS: ET-26HCl has anesthetic potency and hemodynamic stability similar to etomidate,but it caused less adrenocortical hormone synthesis suppression than etomidate and faster spatial orientation recovery from anesthesia than propofol,which was similar to etomidate.
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