Effect of four potassium channel agonists on bupivacaine-induced toxicity in mice.
The influence of four potassium channel agonists i.e. diazoxide (D), levcromakalim (L), nicorandil (N) and pinacidil (P) on bupivacaine-induced acute toxicity was evaluated by measuring the convulsant activity, the time of latency to convulse and the mortality rate. Four different 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 NMRI 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 were injected with a 50 mg/kg/i.p. single dose of bupivacaine. The convulsant 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.
Gantenbein
M
M
Laboratoire de Pharmacologie Médicale, Faculté de Médecine de Marseille, France.
Attolini
L
L
Bruguerolle
B
B
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002045:Bupivacaine / Q000633:toxicity*; D019806:Cromakalim; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D020110:Pinacidil; D015221:Potassium Channels / Q000819:agonists*; D011758:Pyrroles / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D020110:Pinacidil; D003981:Diazoxide; D002045:Bupivacaine