Potassium channel agonists modify the local anaesthetic activity of bupivacaine in mice

Purpose: The mechanisms of action of focal anaesthetics and potassium channel agonists (PCAs) may interfere by acting in a direct or indirect manner on the same ion channels. In a previously reported study, the bupivacaine-induced mortality was shown to be modified in different ways by four PCAs tested (diazoxide (D), levcromakalim (L), nicorandil (N) and pinacidil (P)) since bupivacaine-induced mortality was increased by high doses of P and L, decreased by N and stayed unchanged by D. The present study was designed to document the changes in bupivacaine (B) focal anaesthetic activity in mice after a single injection of one of the four PCAs (D, L, N and P). Methods: Each PCA was tested at three different dosages. Controls received saline. The local anaesthetic activity was evaluated using sciatic nerve blockade. After Injection of bupivacaine in the region of the sciatic nerve, the local anaesthetic activity was estimated as the loss of motor control of the injected limb. Results: PCA treatment increased (P = 0.0001) the time needed for recovery from bupivacaine-induced focal anaesthesia. The area under the effect vs time curve, assessing the total anaesthetic effect, was greater for N (P = 0.0016) and P (P = 0.038) but not for L (P = 0.11). Compared with controls, the maximal effect (Emax) was less for D (P = 0.009) and N (P = 0.038) but nob for L (P = 0.185) or P (P = 0.45) treated groups. The injection of the PCA in the region of the sciatic nerve of the right hindlimb did not induce any alteration of the motor activity of the injected limb. Conclusion: The four PCAs decreased the maximal local anaesthetic effect and increased the duration of action of bupivacaine.