Effects of i.v. anaesthetic agents and halothane on [3H]tetracaine binding to rat cerebrocortical membranes. 1998

M Kudo, and T Kudo, and D G Lambert
University Department of Anaesthesia, Leicester Royal Infirmary.

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.

UI MeSH Term Description Entries
D008566 Membranes Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures. Membrane Tissue,Membrane,Membrane Tissues,Tissue, Membrane,Tissues, Membrane
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D006221 Halothane A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178) 1,1,1-Trifluoro-2-Chloro-2-Bromoethane,Fluothane,Ftorotan,Narcotan
D000779 Anesthetics, Local Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate. Anesthetics, Conduction-Blocking,Conduction-Blocking Anesthetics,Local Anesthetic,Anesthetics, Topical,Anesthetic, Local,Anesthetics, Conduction Blocking,Conduction Blocking Anesthetics,Local Anesthetics,Topical Anesthetics
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding
D013748 Tetracaine A potent local anesthetic of the ester type used for surface and spinal anesthesia. Tetrakain,Amethocaine,Ametop,Dicaine,Pantocaine,Pontocaine,Tetracaine Monohydrochloride,Tetrracaine Hydrochloride,Hydrochloride, Tetrracaine
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

Related Publications

M Kudo, and T Kudo, and D G Lambert
September 1985, British journal of pharmacology,
M Kudo, and T Kudo, and D G Lambert
January 2000, Journal of anesthesia,
M Kudo, and T Kudo, and D G Lambert
March 1986, Journal of neurochemistry,
M Kudo, and T Kudo, and D G Lambert
April 1987, Pharmacology, biochemistry, and behavior,
M Kudo, and T Kudo, and D G Lambert
August 1979, British journal of anaesthesia,
M Kudo, and T Kudo, and D G Lambert
December 1989, Nihon Naibunpi Gakkai zasshi,
M Kudo, and T Kudo, and D G Lambert
January 1979, Advances in experimental medicine and biology,
M Kudo, and T Kudo, and D G Lambert
April 1991, Journal of cardiovascular pharmacology,
Copied contents to your clipboard!