Interaction between flumazenil and the anesthetic effects of hexobarbital in the rat.

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Korkmaz S, Ljungblad E, Wahlstrom G

Interaction between flumazenil and the anesthetic effects of hexobarbital in the rat.

Brain Res. 1995 Apr 10;676(2):371-7.

PubMed ID
7614008 [ View in PubMed
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Abstract

Interaction between flumazenil, a substance regarded mainly as a benzodiazepine antagonist, and an intravenous anesthetic barbiturate, hexobarbital, was investigated by using an electroencephalography threshold test in male rats. Flumazenil 10 mg/kg given as pretreatment reduced the threshold dose of hexobarbital approximately 20% indicating a synergistic interaction. Similar effects were obtained with the agonists, diazepam 20 mg/kg and lorazepam 2 mg/kg. Dose-response curve for flumazenil (2.5-10 mg/kg) was determined with the same technique and hexobarbital concentrations were analysed in serum and several brain regions at the threshold by high pressure liquid chromatography. Flumazenil 10 mg/kg pretreated group showed a different pattern of distribution of hexobarbital into the tested brain regions indicating a pharmacokinetic interaction. Low concentrations of hexobarbital in the brainstem which were negatively correlated with the dose of flumazenil indicate a pharmacodynamic interaction which could be due to partial agonistic intrinsic activity of flumazenil, usually seen at much higher doses.

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