title: 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.
authors.affiliation: University Department of Anaesthesia, Leicester Royal Infirmary.
authors.forename: M
authors.initials: M
authors.lastname: Kudo
authors.forename: T
authors.initials: T
authors.lastname: Kudo
authors.forename: D G
authors.initials: DG
authors.lastname: Lambert
mesh_terms: D018685:Anesthetics, Inhalation / Q000378:metabolism*; D018686:Anesthetics, Intravenous / Q000378:metabolism*; D000779:Anesthetics, Local / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006221:Halothane / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013748:Tetracaine / Q000378:metabolism*
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D013748:Tetracaine; D006221:Halothane