Tonic Blocking Action of Meperidine on Na+ and K+ Channels in Amphibian Peripheral Nerves

Background: Among opioids, meperidine (pethidine) also shows local anesthetic activity when applied locally to peripheral nerve fibers and has been used for this effect in the clinical setting for regional anesthesia. This study investigated the blocking effects of meperidine on different ion channels in peripheral nerves.

Methods: Experiments were conducted using the outside-out configuration of the patch-clamp method applied to enzymatically prepared peripheral nerve fibers of Xenopus laevis. Half-maximal inhibiting concentrations were determined for Na+ channels and different K+ channels by nonlinear least-squares fitting of concentration-inhibition curves, assuming a one-to-one reaction.

Results: Externally applied meperidine reversibly blocked all investigated channels in a concentration-dependent manner, i.e., voltage-activated Na+ channel (half-maximal inhibiting concentration, 164 [mu]M), delayed rectifier K+ channels (half-maximal inhibiting concentration, 194 [mu]M), the calcium-activated K+ channel (half-maximal inhibiting concentration, 161 [mu]M), and the voltage-independent flicker K+ channel (half-maximal inhibiting concentration, 139 [mu]M). Maximal block in high concentrations of meperidine reached 83% for delayed rectifier K+ channels and 100% for all other channels. Meperidine blocks the Na+ channel in the same concentration range as the local anesthetic agent lidocaine (half-maximal inhibiting concentration, 172 [mu]M) but did not compete for the same binding site as evaluated by competition experiments. Low concentrations of meperidine (1 nM to 1 [mu]M) showed no effects on Na+ channels. The blockade of Na+ and delayed rectifier K+ channels could not be antagonized by the addition of naloxone.