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The effect of benzodiazepine receptor antagonism by flumazenil on the MAC of halothane in the rat.

The effects of a benzodiazepine receptor agonist and an antagonist on the MAC of halothane required to achieve anesthesia were evaluated to explore the possible functional interaction between halothane and the benzodiazepine receptor. Rats were anesthetized with halothane and then administered midazolam (a benzodiazepine agonist) and/or flumazenil (a benzodiazepine antagonist). Flumazenil in doses of 0.1 mg/kg and 1.0 mg/kg was found to have no effect on the MAC of halothane. Midazolam (1.0 mg/kg) lowered the MAC of halothane by 37%. This decrease in MAC was inhibited by coadministration of flumazenil. The absence of an increase in the MAC of halothane in the presence of flumazenil suggests that halothane does not interact with the benzodiazepine receptor, directly or indirectly, to produce its anesthetic action.