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Journal of Pharmacology And Experimental Therapeutics, Vol. 120, Issue 1, 75-83, 1957
Copyright © 1957 by American Society for Pharmacology and Experimental Therapeutics

ENZYMATIC OXIDATION OF PENTOBARBITAL AND THIOPENTAL

Jack R. Cooper 1 and Bernard B. Brodie 1

1 Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Public Health Service, U. S. Department of Health, Education, and Welfare, Bethesda, Maryland

Pentobarbital and its thio-analogue thiopental are oxidized in rabbit liver homogenates. Thiopental, in addition, is metabolized to a lesser extent in other tissues, especially kidney and brain.

Pentobarbital is converted to an alcohol with the hydroxyl group on carbon three of the sidechain and an acid with the carboxyl group on carbon four. These metabolites are formed in about equal amounts. Thiopental appears to yield mainly the corresponding acid and a small amount of the alcohol.

As with the oxidation of a number of other drug metabolic transformations, the oxidative system for the barbiturates occurs in the microsomes and requires TPNH and oxygen. The microsomal systems cause little or no splitting of the malonylurea ring.

The oxidation of pentobarbital and thiopental seems to be carried out by different catalytic mechanisms.

Submitted on December 19, 1956






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Copyright © 1957 by the American Society for Pharmacology and Experimental Therapeutics.