A benzodiazepine receptor antagonist improves emergence of mice from halothane anaesthesia.
The benzodiazepine receptor antagonist, flumazenil, at a dose of 10 mg/kg given intraperitoneally to mice, had no effect on the minimum air concentration (MAC-50) of halothane causing anesthesia in 50% of the animals and which was 1.0% by volume of the inhaled air. Diazepam, 10 mg/kg, potentiated the effect of halothane. When the mice had been pretreated with diazepam and flumazenil, 10 mg/kg or 20 mg/kg, partial but not complete reversal of the potentiating effect of diazepam was observed, minimum air concentration values being 0.6% after diazepam alone and 0.8% after diazepam and flumazenil. However, mice pretreated intraperitoneally with flumazenil, in the concentration range 1-10 mg/kg, delivered as a solution in polyethylene glycol-Intralipid vehicle or as a suspension in saline, recovered control levels of spontaneous motor activity much faster than in the absence of flumazenil, on emergence from halothane-induced anaesthesia. In this range, the effect was not dose-dependent. These findings suggest that some of the effects of halothane are mediated at the level of the benzodiazepine receptor.
Geller
E
E
Department of Anesthesiology and Intensive Care, Tel Aviv Medical Center, Israel.
Schiff
B
B
Halpern
P
P
Speiser
Z
Z
Cohen
S
S
D000758:Anesthesia; D000818:Animals; D005442:Flumazenil / Q000494:pharmacology*; D006221:Halothane; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects*
D011963:Receptors, GABA-A; D005442:Flumazenil; D006221:Halothane