Kudo M, Kudo T, Lambert D G
University Department of Anaesthesia, Leicester Royal Infirmary.
Br J Anaesth. 1998 Jan;80(1):73-6. doi: 10.1093/bja/80.1.73.
In an attempt to determine if there is any overlap in local and general anaesthetic binding sites, we have examined the effects of thiopental, phenobarbital, pentobarbital, propofol, ketamine (racemic and R(+)/S(-)), alfaxalone, etomidate and halothane on [3H]tetracaine binding to rat cerebrocortical membranes. Membranes were prepared in Tris HCI 50 mmol litre-1, pH 7.4, by homogenization and centrifugation. Binding assays were performed in 1-ml volumes of Tris HCI buffer at room temperature or 37 degrees C for halothane. Binding of [3H]tetracaine was displaced dose-dependently by unlabelled tetracaine with a mean pIC50 value of 6.91 (SEM 0.07) (123 nmol litre-1). With the exception of propofol (at high concentrations), all i.v. anaesthetic agents failed to displace the binding of [3H]tetracaine. In contrast, halothane produced a dose-dependent and statistically significant reduction in total [3H]tetracaine binding at clinically achievable concentrations (0.289, 0.885 and 1.484 mmol litre-1 equivalent to 1.0, 3.1 and 5.1 rat MAC) without markedly affecting the pIC50. Collectively these data may suggest some overlap in the binding sites for [3H]tetracaine and volatile but not i.v. general anaesthetic agents.
为了确定局部麻醉药和全身麻醉药的结合位点是否存在重叠，我们研究了硫喷妥钠、苯巴比妥、戊巴比妥、丙泊酚、氯胺酮（消旋体和R(+)/S(-)）、阿法沙龙、依托咪酯和氟烷对[3H]丁卡因与大鼠大脑皮质膜结合的影响。通过匀浆和离心在50 mmol/L Tris HCl（pH 7.4）中制备膜。在室温或氟烷的37℃下，在1 ml Tris HCl缓冲液中进行结合测定。未标记的丁卡因以剂量依赖性方式取代[3H]丁卡因的结合，平均pIC50值为6.91（标准误0.07）（123 nmol/L）。除丙泊酚（高浓度时）外，所有静脉麻醉药均未能取代[3H]丁卡因的结合。相反，在临床可达到的浓度（0.289、0.885和1.484 mmol/L，相当于1.0、3.1和5.1大鼠最低肺泡有效浓度）下，氟烷使总[3H]丁卡因结合呈剂量依赖性且具有统计学意义的降低，而对pIC50没有明显影响。总体而言，这些数据可能表明[3H]丁卡因与挥发性全身麻醉药而非静脉全身麻醉药的结合位点存在一些重叠。
