The Anesthetic Effects of Etomidate: Species-Specific Interaction with 2-Adrenoceptors

Peter H. Tonner, MD* BACKGROUND: The IV anesthetic, etomidate, has structural and clinical similarities to specific 2-adrenoceptor agonists such as dexmedetomidine. We investigated whether the sedative effects of etomidate may be mediated by 2-adrenoceptors. METHODS: The anesthetic potency of etomidate (1–20 M) was determined in Xenopus laevis tadpoles in the absence and presence of the specific 2-adrenoceptor antagonist atipamezole (10 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 2A-adrenoceptor gene ( 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 M; slope: 2.6 0.3) to 8.4 0.4 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 2A-KO animals compared with WT mice. CONCLUSIONS: The sedative effects of etomidate exhibit a species-specific interaction with 2-adrenoceptors. Although the decrease in potency of etomidate by atipamezole may be caused by an interaction with 2-adrenoceptors in X. laevis tadpoles, results in mice indicate that the hypnotic effect of etomidate does not require 2-adrenoceptors. (Anesth Analg 2007;105:1644–9)