An Etomidate Analogue With Less Adrenocortical Suppression, Stable Hemodynamics, and Improved Behavioral Recovery in Rats.

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 up-and-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 recover 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

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