The anesthetic effects of etomidate:: Species-specific interaction with α2-adrenoceptors

BACKGROUND: The IV anesthetic, etomidate, has structural and clinical similarities to specific alpha(2)-adrenoceptor agonists such as dexmedetomidine. We investigated whether the sedative effects of etomidate may be mediated by alpha(2)-adrenoceptors. METHODS: The anesthetic potency of etomidate (1-20 mu M) was determined in Xenopus laevis tadpoles in the absence and presence of the specific alpha(2)-adrenoceptor antagonist atipamezole (10 mu M). Anesthesia was defined as loss of righting reflex. Nonlinear logistic regression curves were fitted to the data and half-maximal effective concentrations and the slopes of the curves were calculated. Additionally, sedative/hypnotic effects of etomidate (8 mg/kg IP) were studied by rotarod test in wild-type (WT) mice and mice carrying targeted deletions of the alpha(2A)-adrenoceptor gene (alpha(2A)-KO). Data are presented as mean +/- SEM. RESULTS: The fraction of anesthetized tadpoles increased with increasing concentrations of etomidate. Atipamezole significantly increased the half-maximal effective concentration of etomidate (4.5 +/- 0.2 mu M; slope: 2.6 +/- 0.3) to 8.4 +/- 0.4 mu M (slope: 2.3 +/- 0.3). Etomidate resulted in time-dependent sedative effects in all mice, as assessed by rotarod performance. In WT mice, the sedative effects of etomidate were not decreased by atipamezole (2 mg/kg). Consistently, etomidate-induced sedation was not reduced in alpha(2A)-KO animals compared with WT mice. CONCLUSIONS: The sedative effects of etomidate exhibit a species-specific interaction with alpha(2)-adrenoceptors. Although the decrease in potency of etomidate by atipamezole may be caused by an interaction with alpha(2)-adrenoceptors in X. laevis tadpoles, results in mice indicate that the hypnotic effect of etomidate does not require alpha(2)-adrenoceptors.