Effects of i.v. anaesthetic agents and halothane on [3H]tetracaine binding to rat cerebrocortical membranes.

Abstract

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.