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Journal of Pharmacology And Experimental Therapeutics, Vol. 172, Issue 1, 18-32, 1970
Copyright © 1970 by American Society for Pharmacology and Experimental Therapeutics

THE EFFECTS OF pH GRADIENTS ON THE UPTAKE AND DISTRIBUTION OF C14-PROCAINE AND LIDOCAINE IN INTACT AND DESHEATHED SCIATIC NERVE TRUNKS

GEORGE E. STROBEL 1 and C. PAUL BIANCHI 1

1 Departments of Anesthesiology and Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

The effects of pH gradients on the uptakes amphibian nerve trunks is greater than in solutions with which they have been equilibrated, more so at pH 8.2 than at pH 7.2, and more so in intact than in desheathed preparations at pH 8.2. The presence of a pH gradient at the perineural sheath of an intact frog sciatic nerve in an alkaline media can be demonstrated by measurements of the tissue uptake of the weak acid 5,5-dimethyl-2,4-oxazolidinedione. pH gradients between extracellular and intracellular water phases, large enough to concentrate the cationic form of the local anesthetic at sites at a lower pH within the nerve tissue, can be demonstrated even in completely desheathed sciatic nerves. The apparent diffusion coefficients for the drugs in nerve tissue were estimated from washout curves. The washout of lidocaine is faster than procaine. The washout of either drug is faster at a neutral rather than alkaline pH, which demonstrates that pH gradients influence rates of diffusion as well as equilibrium con centrations of ionizable drugs in tissues.

Submitted on August 4, 1969
Accepted on October 29, 1969




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