Abstract
Three compounds, α-tocopherol phosphate (α-TPh), tetraethylthiuram disulfide (TETD), and β-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 α-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 α-TPh were investigated. It was found that α-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 α-TPh per se.
Footnotes
- Received April 2, 1955.
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