The inhibitory effects of local anesthetics on superoxide generation of neutrophils correlate with their partition coefficients.

Lidocaine and tetracaine suppress superoxide anion (O2-) generation of neutrophils. We examined the effects of eight local anesthetics on O2- generation in human neutrophils and searched for a potential relationship between the biological activities and the physicochemical properties of presently available eight local anesthetics. Human neutrophils incubated with local anesthetic and a Cypridina luciferin analog as a O2(-)-specific chemiluminescence probe were stimulated by phorbol ester. The chemiluminescence development based on O2- generation was monitored by a luminometer. All of the tested local anesthetics suppressed O2- generation in a concentration-dependent manner. The concentration of each of eight local anesthetics that produced 50% inhibition of peak chemiluminescence (IC50) had a rank order of dibucaine < tetracaine < bupivacaine < ropivacaine < procaine < mepivacaine < lidocaine = prilocaine. A linear relationship was obtained between IC50 values and the values of logarithm of partition coefficient (log P) of eight local anesthetics; log (IC50 in molarity) = -1.252 - 0.514 x log P, r2 = 0.891, P < 0.001. Unlike with staurosporine, which inhibits protein kinase C (PKC), no effect was observed on the O2- generation in the presence of tetrodotoxin (TTX), veratridine (VTD), or amiloride. These results suggest that the inhibitory effects of local anesthetics on O2- generation of neutrophils are predicted by physicochemical properties of the drugs, especially partition coefficients.