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Journal of Pharmacology And Experimental Therapeutics, Vol. 115, Issue 2, 240-249, 1955
Copyright © 1955 by American Society for Pharmacology and Experimental Therapeutics

STUDIES ON THE POTENTIATION OF THIOPENTAL

Joseph H. Mirsky 1 and Nicholas J. Giarman 1

1 Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut

Three compounds, agr-tocopherol phosphate (agr-TPh), tetraethylthiuram disulfide (TETD), and beta-diethylaminoethyldiphenylpropyl acetate (SKF-525A) have been investigated for their influence on the duration of depression of the central nervous system produced by thiopental in various animal species. It was found that a prolongation of the duration of thiopental-induced depression is elicited by agr-TPh in mice and rats, but not in dogs or rabbits; by TETD in rats; and by SKF-525A in mice and rats.

Several possible mechanisms of the potentiating action of agr-TPh were investigated. It was found that agr-TPh significantly influences the amount of thiopental appearing in the plasma, but not in the fat or brain; it inhibits the oxidation of thiopental by liver slices of the rat; and it exerts a slight antagonistic action on Metrazol convulsions. It has been concluded that the potentiating mechanism involves a combination of two factors: primarily an inhibition of the metabolic oxidation of thiopental; and a secondary, slight depression of the central nervous system by the agr-TPh per se.

Submitted on April 2, 1955




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