FLUMAZENIL DOES NOT ANTAGONIZE HALOTHANE, THIAMYLAL OR PROPOFOL ANESTHESIA IN RATS

We have studied the effects of flumazenil on sleep time and EEG in rats anaesthetized with 1.5% halothane, propofol 20 mg kg-1, thiamylal 30 mg kg-1, or combinations of diazepam 5 mg kg-1 and anaesthetic agents. We also studied the effects of flumazenil 0.3, 3 and 30 mg kg-1 on behaviour and EEG. Flumazenil 0.3 and 3 mg kg-1 alone had no effect on behaviour or EEG, but flumazenil 30 mg kg-1 had depressive effects similar to those of diazepam on behaviour and EEG. Flumazenil 0.3, 3 and 30 mg kg-1 iv., antagonized the effects of diazepam 10 mg kg-1 iv. on behaviour and EEG. Flumazenil had no antagonistic effect on sleep time induced by anaesthetic agents, but flumazenil 30 mg kg-1 potentiated propofol-induced anaesthesia. Flumazenil did not affect anaesthesia-induced EEG changes. Diazepam 5 mg kg-1 potentiated anaesthesia. Flumazenil antagonism of diazepam potentiation varied with anaesthetic agent: flumazenil 0.3 mg kg-1 antagonized diazepam action in halothane anaesthesia, but 30 mg kg-1 was required in propofol anaesthesia; this large dose was insufficient in thiamylal anaesthesia.