Vanlersberghe C, Camu F
Department of Anesthesiology, University of Brussels V.U.B. Medical Center, Laarbeeklaan 101, B-1090, Brussels, Belgium.
Handb Exp Pharmacol. 2008(182):267-82. doi: 10.1007/978-3-540-74806-9_13.
It is today generally accepted that anesthetics act by binding directly to sensitive target proteins. For certain intravenous anesthetics, such as propofol, barbiturates, and etomidate, the major target for anesthetic effect has been identified as the gamma-aminobutyric acid type A (GABA(A)) receptor, with particular subunits playing a crucial role. Etomidate, an intravenous imidazole general anesthetic, is thought to produce anesthesia by modulating or activating ionotropic Cl(-)-permeable GABA(A) receptors. For the less potent steroid anesthetic agents the picture is less clear, although a relatively small number of targets have been identified as being the most likely candidates. In this review, we summarize the most relevant clinical and experimental pharmacological properties of these intravenous anesthetics, the molecular targets mediating other endpoints of the anesthetic state in vivo, and the work that led to the identification of the GABA(A) receptor as the key target for etomidate and aminosteroids.
如今人们普遍认为，麻醉剂通过直接与敏感靶蛋白结合发挥作用。对于某些静脉麻醉剂，如丙泊酚、巴比妥类药物和依托咪酯，麻醉作用的主要靶点已被确定为γ-氨基丁酸A型（GABA(A)）受体，特定亚基起着关键作用。依托咪酯是一种静脉注射咪唑类全身麻醉剂，被认为通过调节或激活离子型Cl(-)渗透性GABA(A)受体产生麻醉作用。对于效力较低的类固醇麻醉剂，情况则不太清楚，尽管已确定相对较少的靶点是最有可能的候选靶点。在本综述中，我们总结了这些静脉麻醉剂最相关的临床和实验药理学特性、介导体内麻醉状态其他终点的分子靶点，以及导致将GABA(A)受体确定为依托咪酯和氨基类固醇关键靶点的研究工作。
