Zimmerman S A, Jones M V, Harrison N L
Department of Anesthesia and Critical Care, University of Chicago, Illinois.
J Pharmacol Exp Ther. 1994 Sep;270(3):987-91.
Ten general anesthetics of varying structure and potency were investigated for possible modulatory effects on gamma-aminobutyric acid, (GABAA) receptors, using the voltage clamp technique. All 10 anesthetics studied were observed to prolong the duration of responses to exogenously applied GABA recorded in cultured rat hippocampal neurons. These modulatory effects of the anesthetics occurred at pharmacologically relevant concentrations. An excellent correlation exists between drug potency as modulators of the GABAA receptor and anesthetic potency in vivo. These data suggest an alternative interpretation of the historical association between anesthetic potency and lipophilicity. It is proposed that hydrophobic binding sites on ligand-gated ion channel proteins, such as the GABAA receptors, constitute a molecular target site for many general anesthetics.
利用电压钳技术，研究了十种结构和效力各异的全身麻醉剂对γ-氨基丁酸（GABAA）受体的潜在调节作用。在所研究的全部十种麻醉剂中，均观察到它们可延长培养的大鼠海马神经元中对外源性施加的GABA反应的持续时间。这些麻醉剂的调节作用发生在药理学相关浓度下。作为GABAA受体调节剂的药物效力与体内麻醉效力之间存在极佳的相关性。这些数据为麻醉效力与亲脂性之间的历史关联提供了另一种解释。有人提出，配体门控离子通道蛋白（如GABAA受体）上的疏水结合位点构成了许多全身麻醉剂的分子靶点。
