Dependence of lidocaine potency on pH and PCO2.
Lidocaine solutions with different concentrations of CO2, NaOH, and HCl in two buffering systems were applied to frog sciatic nerves. The peak of the compound action potential (APc) and the firing threshold for single axons were measured. The amount of lidocaine required at steady state to double the firing threshold of single fibers or to reduce the peak of the APc by 40% was used as the index of potency. Acidification with CO2 increased potency (less lidocaine was needed to achieve either criterion), whereas acidification with HCl diminished potency, as compared with alkaline conditions. These results were true whether or not the perineurium was present. Frequency-dependent block (Bf) increased in acid conditions produced by CO2, whereas Bf was less under acid conditions produced with HCl (P less than 0.02). The experiments indicate that CO2 potentiates conduction block with lidocaine either by a direct effect on the membrane or by its indirect action on intracellular pH, but not from effects on the extracellular pH.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D002021:Buffers; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D006851:Hydrochloric Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007552:Isotonic Solutions; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D009431:Neural Conduction / Q000187:drug effects; D011894:Rana pipiens; D000077331:Ringer's Solution; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology; D012996:Solutions
D002021:Buffers; D007552:Isotonic Solutions; D012996:Solutions; D002245:Carbon Dioxide; D000077331:Ringer's Solution; D008012:Lidocaine; D006851:Hydrochloric Acid