EFFECT OF 4 POTASSIUM CHANNEL AGONISTS ON BUPIVACAINE-INDUCED TOXICITY IN MICE

The influence of four potassium channel agonists i.e. diazoxide (D), l evcromakalim (L), nicorandil (N) and pinacidil (P) on bupivacaine-indu ced acute toxicity was evaluated by measuring the convulsant activity, the time of latency to convulse and the mortality rate. Four differen t dosages (i.e. 0.1, 1, 10 and 100 mg/kg/i.p. for D, N and P and 0.01, 0.1, 1 and 5 mg/kg/i.p. for L) were injected to a total of 200 male N MRI adult mice : 16 groups of 10 mice each were previously treated by a single i.p. dose of each potassium channel agonist while controls (n = 40) received saline injection. Thus, 15 minutes later, all groups w ere injected with a 50 mg/kg/i.p. single dose of bupivacaine. The conv ulsant activity of bupivacaine was significantly modified by only high doses of L in a dose-dependent manner. Compared to the controls, the period of latency was significantly increased for most of the doses of P, N, D and L in a dose dependent manner for L and P. The anesthetic- induced mortality (47.5 % for controls) was not significantly modified by D, but decreased by N and increased by high doses of L and P which is probably related to a delayed mortality.