Flumazenil and bupivacaine-induced toxicity: inverse agonist type activity

The purpose of this study was to investigate the influence of flumazenil on bupivacaine-induced acute toxicity, 10 groups of mice were previously treated by a 1, 0.5, 0.25 and 0.125 mg/kg single dose of flumazenil or saline 15 minutes before an injection of bupivacaine (50 mg/kg: exp. 1 and 60 mg/kg: exp.2). The convulsant activity, the period of latency to convulse and the induced mortality were assessed in each group. The bupivacaine-induced mortality was increased by flumazenil. Also, the convulsant activity was increased by flumazenil and the period of latency to convulse was proportionally decreased with increasing doses of flumazenil for the two tested doses of bupivacaine.