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lüll Clinical and molecular pharmacology of etomidate Forman SAAnesthesiology 2011[Mar]; 114 (3): 695-707This review focuses on the unique clinical and molecular pharmacologic features of etomidate. Among general anesthesia induction drugs, etomidate is the only imidazole, and it has the most favorable therapeutic index for single-bolus administration. It also produces a unique toxicity among anesthetic drugs: inhibition of adrenal steroid synthesis that far outlasts its hypnotic action and that may reduce survival of critically ill patients. The major molecular targets mediating anesthetic effects of etomidate in the central nervous system are specific gamma-aminobutyric acid type A receptor subtypes. Amino acids forming etomidate binding sites have been identified in transmembrane domains of these proteins. Etomidate binding site structure models for the main enzyme mediating etomidate adrenotoxicity have also been developed. Based on this deepening understanding of molecular targets and actions, new etomidate derivatives are being investigated as potentially improved sedative-hypnotics or for use as highly selective inhibitors of adrenal steroid synthesis.|Adrenal Cortex Hormones/antagonists & inhibitors[MESH]|Anesthesia, Intravenous[MESH]|Anesthetics, Intravenous/administration & dosage/*pharmacology/therapeutic use[MESH]|Animals[MESH]|Animals, Genetically Modified/physiology[MESH]|Etomidate/administration & dosage/adverse effects/*pharmacology/therapeutic use[MESH]|Hemodynamics/drug effects[MESH]|Humans[MESH]|Hypnotics and Sedatives/administration & dosage/adverse effects/*pharmacology/therapeutic use[MESH]|Mutation/physiology[MESH]|Receptors, Adrenergic/drug effects[MESH]|Receptors, GABA-A/drug effects/genetics/physiology[MESH]|Steroids/biosynthesis[MESH] |