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Anesthesiology
2010 Mar 01;1123:637-44. doi: 10.1097/ALN.0b013e3181cf40ed.
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Carboetomidate: a pyrrole analog of etomidate designed not to suppress adrenocortical function.
Cotten JF
,
Forman SA
,
Laha JK
,
Cuny GD
,
Husain SS
,
Miller KW
,
Nguyen HH
,
Kelly EW
,
Stewart D
,
Liu A
,
Raines DE
.
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Etomidate is a sedative hypnotic that is often used in critically ill patients because it provides superior hemodynamic stability. However, it also binds with high affinity to 11beta-hydroxylase, potently suppressing the synthesis of steroids by the adrenal gland that are necessary for survival. The authors report the results of studies to define the pharmacology of (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate), a pyrrole analog of etomidate specifically designed not to bind with high affinity to 11beta-hydroxylase. The hypnotic potency of carboetomidate was defined in tadpoles and rats using loss of righting reflex assays. Its ability to enhance wild-type alpha1beta2gamma2l and etomidate-insensitive mutant alpha1beta2M286Wgamma2l human gamma-aminobutyric acid type A receptor activities was assessed using electrophysiologic techniques. Its potency for inhibiting in vitro cortisol synthesis was defined using a human adrenocortical cell assay. Its effects on in vivo hemodynamic and adrenocortical function were defined in rats. Carboetomidate was a potent hypnotic in tadpoles and rats. It increased currents mediated by wild-type but not etomidate-insensitive mutant gamma-aminobutyric acid type A receptors. Carboetomidate was a three orders of magnitude less-potent inhibitor of in vitro cortisol synthesis by adrenocortical cells than was etomidate. In rats, carboetomidate caused minimal hemodynamic changes and did not suppress adrenocortical function at hypnotic doses. Carboetomidate is an etomidate analog that retains many beneficial properties of etomidate, but it is dramatically less potent as an inhibitor of adrenocortical steroid synthesis. Carboetomidate is a promising new sedative hypnotic for potential use in critically ill patients in whom adrenocortical suppression is undesirable.
Absalom,
Adrenocortical function in critically ill patients 24 h after a single dose of etomidate.
1999, Pubmed
Absalom,
Adrenocortical function in critically ill patients 24 h after a single dose of etomidate.
1999,
Pubmed
Allolio,
Nonhypnotic low-dose etomidate for rapid correction of hypercortisolaemia in Cushing's syndrome.
1988,
Pubmed
Annane,
ICU physicians should abandon the use of etomidate!
2005,
Pubmed
Ayub,
Inhibition of human adrenal steroidogenic enzymes in vitro by imidazole drugs including ketoconazole.
1989,
Pubmed
Bloomfield,
Etomidate and fatal outcome--even a single bolus dose may be detrimental for some patients.
2006,
Pubmed
Cotten,
Methoxycarbonyl-etomidate: a novel rapidly metabolized and ultra-short-acting etomidate analogue that does not produce prolonged adrenocortical suppression.
2009,
Pubmed
,
Xenbase
Criado,
Induction of anaesthesia with etomidate: haemodynamic study of 36 patients.
1980,
Pubmed
Cuthbertson,
The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock.
2009,
Pubmed
de Jong,
Etomidate suppresses adrenocortical function by inhibition of 11 beta-hydroxylation.
1984,
Pubmed
Diago,
Anti-adrenal action of a subanaesthetic dose of etomidate.
1988,
Pubmed
Ebert,
Sympathetic responses to induction of anesthesia in humans with propofol or etomidate.
1992,
Pubmed
Fallo,
Effects of taxol on the human NCI-H295 adrenocortical carcinoma cell line.
1996,
Pubmed
Fallo,
Paclitaxel is an effective antiproliferative agent on the human NCI-H295 adrenocortical carcinoma cell line.
1998,
Pubmed
Fassnacht,
New mechanisms of adrenostatic compounds in a human adrenocortical cancer cell line.
2000,
Pubmed
Fragen,
Effects of etomidate on hormonal responses to surgical stress.
1984,
Pubmed
Gooding,
Cardiovascular and pulmonary responses following etomidate induction of anesthesia in patients with demonstrated cardiac disease.
1979,
Pubmed
Hildreth,
Adrenal suppression following a single dose of etomidate for rapid sequence induction: a prospective randomized study.
2008,
Pubmed
Husain,
2-(3-Methyl-3H-diaziren-3-yl)ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate: a derivative of the stereoselective general anesthetic etomidate for photolabeling ligand-gated ion channels.
2003,
Pubmed
,
Xenbase
Hutzler,
Inhibition of cytochrome P450 3A4 by a pyrimidineimidazole: Evidence for complex heme interactions.
2006,
Pubmed
Jackson,
Should we use etomidate as an induction agent for endotracheal intubation in patients with septic shock?: a critical appraisal.
2005,
Pubmed
Lamberts,
Differential effects of the imidazole derivatives etomidate, ketoconazole and miconazole and of metyrapone on the secretion of cortisol and its precursors by human adrenocortical cells.
1987,
Pubmed
Ledingham,
Influence of sedation on mortality in critically ill multiple trauma patients.
1983,
Pubmed
Locuson,
Visible spectra of type II cytochrome P450-drug complexes: evidence that "incomplete" heme coordination is common.
2007,
Pubmed
Ouellet,
Mycobacterium tuberculosis CYP130: crystal structure, biophysical characterization, and interactions with antifungal azole drugs.
2008,
Pubmed
Roumen,
Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics.
2007,
Pubmed
Rüsch,
Gating allosterism at a single class of etomidate sites on alpha1beta2gamma2L GABA A receptors accounts for both direct activation and agonist modulation.
2004,
Pubmed
,
Xenbase
Sarkar,
Hemodynamic responses to etomidate on induction of anesthesia in pediatric patients.
2005,
Pubmed
Scott,
Structure of mammalian cytochrome P450 2B4 complexed with 4-(4-chlorophenyl)imidazole at 1.9-A resolution: insight into the range of P450 conformations and the coordination of redox partner binding.
2004,
Pubmed
Seward,
Crystal structure of the Mycobacterium tuberculosis P450 CYP121-fluconazole complex reveals new azole drug-P450 binding mode.
2006,
Pubmed
Siegwart,
Molecular determinants for the action of general anesthetics at recombinant alpha(2)beta(3)gamma(2)gamma-aminobutyric acid(A) receptors.
2002,
Pubmed
Vinclair,
Duration of adrenal inhibition following a single dose of etomidate in critically ill patients.
2008,
Pubmed
Wagner,
Inhibition of adrenal steroidogenesis by the anesthetic etomidate.
1984,
Pubmed
Waud,
On biological assays involving quantal responses.
1972,
Pubmed
Yano,
Synthetic inhibitors of cytochrome P-450 2A6: inhibitory activity, difference spectra, mechanism of inhibition, and protein cocrystallization.
2006,
Pubmed
Zolle,
New selective inhibitors of steroid 11beta-hydroxylation in the adrenal cortex. Synthesis and structure-activity relationship of potent etomidate analogues.
2008,
Pubmed
