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ANESTHETIC PHARMACOLOGY

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

Andrea Paris, MD^*, Lutz Hein, MD, Marc Brede, MD, Philipp-Alexander Brand, MD^*, Jens Scholz, MD^*, and Peter H. Tonner, MD^*

From the *Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel; Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Freiburg im Breisgau; and Department of Anaesthesia and Critical Care, University of Wuerzburg Hospitals, Wuerzburg, Germany.

Address correspondence and reprint requests to Andrea Paris, MD, Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel Schwanenweg 21, D-24105 Kiel, Germany. Address e-mail to paris{at}anaesthesie.uni-kiel.de.

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 µM) was determined in Xenopus laevis tadpoles in the absence and presence of the specific ₂-adrenoceptor antagonist atipamezole (10 µM). 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 µM; slope: 2.6 ± 0.3) to 8.4 ± 0.4 µM (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.