The Impulse-Blocking Concentrations of Anesthetics, Alcohols, Anticonvulsants, Barbiturates, and Narcotics on Phrenic and Sciatic Nerves

Abstract

(1) The nerve-blocking potencies of anesthetics, alcohols, tranquilizers, antidepressants, anticonvulsants, barbiturates, and narcotics were obtained on the rat phrenic nerve and the sciatic nerves of the frog and the rat. Skou's second method for equilibrium blockade was used, and complete dose–response curves were obtained on the height of the compound action potential.(2) Uncharged drugs (alcohols, urethane) and acidic drugs (barbiturates, diphenylhydantoin) caused half blockade of the phrenic nerve (11 μm diameter fibers) at concentrations about 25–35% of those causing half blockade of sciatic nerve (16 μm fibers).(3) Tertiary amines (procaine, spirosuccinimide enantiomers, chlorpromazine, haloperidol, trifluperidol, methadone, and naloxone) produced half blockade of the phrenic nerve at concentrations about 10% of those producing half blockade of the sciatic nerve. Frog and rat sciatic C50% block values (i.e. the drug concentration that reduced the compound action potential by 50%) were the same.(4) The phrenic C50% block value for tetrodotoxin was 7.1 times higher than that for the sciatic nerve.(5) The phrenic C50% blockvalues of the neutral and acidic drugs (together as a group) correlated inversely with the membrane/buffer partition coefficients of the drugs, in accordance with the classical Meyer–Overton rule of anesthesia. The phrenic C50% block values for the tertiary amines also correlated inversely with the membrane/buffer partition coefficients. Tetrodotoxin did not fit on these two correlations, and appeared to fall into a category of its own.(6) It was concluded that, whether comparing different nerves or the same nerve at different stages of growth, smaller myelinated fibers required lower nerve-blocking concentrations of drugs.