EFFECTS OF IV ANESTHETIC AGENTS AND HALOTHANE ON [H-3]TETRACAINE BINDING TO RAT CEREBROCORTICAL MEMBRANES

In an attempt to determine if there is any overlap in local and genera l anaesthetic binding sites, we have examined the effects of thiopenta l, phenobarbital, pentobarbital, propofol, ketamine (racemic and R(+)/ S(-)), alfaxalone, etomidate and halothane on [H-3]tetracaine binding to rat cerebrocortical membranes. Membranes were prepared in Tris HCl 50 mmol litre(-1), pH 7.4, by homogenization and centrifugation. Bindi ng assays were performed in 1-ml volumes of Tris HCl buffer at room te mperature or 37 degrees C for halothane. Binding of [H-3]tetracaine wa s displaced dose-dependently by unlabelled tetracaine with a mean pIC( 50),, value of 6.91 (SEM 0.07) (123 nmol litre(-1)). With the exceptio n of propofol (at high concentrations), all i.v. anaesthetic agents fa iled to displace the binding of [H-3]tetracaine. In contrast, halothan e 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 pIC(50).,,. Collectively these data may suggest some overlap in the binding sites for [H-3]tetracain e and volatile but not i.v. general anaesthetic agents.