Background and Goal of Study: 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.

Materials and Methods: The metabolic characteristics of ET-26HCl were investigated in vitro using chromatography in rat plasma and liver homogenates. Anesthesia effect and mean arterial pressure (MAP) was estimated at equivalent doses in the rats. Serum concentration of corticosterone, an adrenocortical hormone, was analyzed. The ability of rats to recover from the sedative-hypnotic effects of the drugs was evaluated using open field and Morris water Maze tests. 

Results and Discussion: The in vitro metabolic experiments showed that the percentage of unmetabolized ET-26HCl remained at 70.2% ± 3.3% in rat liver homogenates and 59.6% ± 3.0% in rat plasma, and that for unmetabolized etomidate remained at 79.9% ± 2.6% in rat liver homogenates and 83.0% ± 12.4% in rat plasma after 60 min. In vivo experiments showed that the potency of ET-26HCl to cause a loss of righting reflex in rats was three times lower than that of etomidate in the rats. Propofol caused a greater decrease in MAP relative to the baseline than did ET-26HCl or etomidate. Serum corticosterone levels following drug administration were significantly higher in the ET-26HCl group than in the etomidate group when measured 15 (P < 0.001), 30 (P < 0.001), and 60 (P = 0.002) min after stimulation with ACTH1~24. Recovery of spatial orientation from anesthesia induced by an intravenous bolus injection was faster with ET-26HCl than with propofol, but recovery of spontaneous activity was slower.

Conclusion(s): 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.

An etomidate analogue with less adrenocortical suppression, stable hemodynamics and improved behavioral recovery in rats