title: The inhibitory effects of local anesthetics on superoxide generation of neutrophils correlate with their partition coefficients.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hattori
authors.forename: S
authors.initials: S
authors.lastname: Dohi
authors.forename: M
authors.initials: M
authors.lastname: Nozaki
authors.forename: M
authors.initials: M
authors.lastname: Niwa
authors.forename: H
authors.initials: H
authors.lastname: Shimonaka
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D013481:Superoxides; D013779:Tetrodotoxin; D014701:Veratridine; D000584:Amiloride; D013755:Tetradecanoylphorbol Acetate