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• W2019904128 abstract "In Brief BACKGROUND: The IV anesthetic, etomidate, has structural and clinical similarities to specific α2-adrenoceptor agonists such as dexmedetomidine. We investigated whether the sedative effects of etomidate may be mediated by α2-adrenoceptors. METHODS: The anesthetic potency of etomidate (1–20 μM) was determined in Xenopus laevis tadpoles in the absence and presence of the specific α2-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 α2A-adrenoceptor gene (α2A-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 α2A-KO animals compared with WT mice. CONCLUSIONS: The sedative effects of etomidate exhibit a species-specific interaction with α2-adrenoceptors. Although the decrease in potency of etomidate by atipamezole may be caused by an interaction with α2-adrenoceptors in X. laevis tadpoles, results in mice indicate that the hypnotic effect of etomidate does not require α2-adrenoceptors. IMPLICATIONS: Etomidate has structural and clinical similarities to α2-adrenoceptor agonists. Atipamezole, an α2-adrenoceptor agonist, significantly increased the half-maximal effective concentration of etomidate in tadpoles. In contrast, the sedative effects of etomidate were not reduced in wild-type or transgenic mice lacking the α2-adrenoceptor subtype. Thus the interaction between etomidate and α2-adrenoceptors is species-specific." @default.
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• W2019904128 date "2007-12-01" @default.
• W2019904128 modified "2023-10-18" @default.
• W2019904128 title "The Anesthetic Effects of Etomidate: Species-Specific Interaction with α2-Adrenoceptors" @default.
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• W2019904128 doi "https://doi.org/10.1213/01.ane.0000286178.98799.cd" @default.
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