当前位置： SCI文献检索 > ANESTHESIOLOGY期刊下所有文献 > Carboetomidate: a pyrrole analog of etomidate designed not to suppress adrenocortical function.

Carboetomidate: a pyrrole analog of etomidate designed not to suppress adrenocortical function.

Abstract：

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Cotten JF,Forman SA,Laha JK,Cuny GD,Husain SS,Miller KW,Nguyen HH,Kelly EW,Stewart D,Liu A,Raines DE

doi

10.1097/ALN.0b013e3181cf40ed

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

637-44

issue

eissn

0003-3022

issn

1528-1175

pii

00000542-201003000-00024

journal_volume

112

pub_type

杂志文章

在线工具

Carboetomidate: a pyrrole analog of etomidate designed not to suppress adrenocortical function.