General anaesthetics and their effects on GABA A receptor desensitization

• Published in: Toxicology letters Vol. 100; pp. 217 - 224
• Main Authors: Orser, B.A., McAdam, L.C., Roder, S., MacDonald, J.F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 23.11.1998
• Subjects: Anesthetics, General - pharmacology; Animals; Desensitization; GABA A receptor function; General anaesthetics; Humans; Kinetics; Models, Biological; Receptors, GABA-A - chemistry; Receptors, GABA-A - drug effects; Synaptic Transmission - drug effects; General anaesthetics; Desensitization; GABA A receptor function
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(98)00188-X

1. Intravenous anaesthetics, including propofol and thiopental have at least three distinct effects on GABA A receptor function. 2. Low concentrations of these drugs enhance the amplitude of currents evoked by sub-saturating concentrations of GABA whereas higher concentrations directly activate the receptor in the absence of GABA. 3. Propofol and some barbiturates also decrease the rate and extent of desensitization as indicated by a prolongation in the decay of currents evoked by saturating concentrations of GABA. 4. In contrast, sedative benzodiazepines that lack general anaesthetic properties do not directly activate the GABA A receptor. 5. In addition, benzodiazepines such as midazolam, have no effect on desensitization when examined in the presence of saturating concentrations of GABA. 6. Here, we discuss the effects of intravenous general anaesthetic on desensitization of the GABA A receptor.