BARBITURATES AND OXIDATIVE-PHOSPHORYLATION

¹ Departments of Pharmacology and Psychiatry, University of Illinois College of Medicine, Chicago 12, Illinois
² Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

The effects of a variety of barbiturates on oxidative-phosphorylation catalyzed by brain and liver mitochondrial preparations are compared to the effect on these reactions of the classical uncoupling agent, dinitrophenol. The barbiturates were shown to dissociate the processes of oxidation and phosphorylation. This uncoupling effect is qualitatively similar to that of dinitrophenol. Quantitatively, dinitrophenol produces effects at lower concentrations and has less effect on oxidation than do the barbiturates. On the whole the effects of the thiobarbiturates resemble those of dinitrophenol more closely than do those of the oxygen barbiturates.

The effects of dinitrophenol and the oxygen barbiturates on the activity of the mitochondrial system can be reversed by washing the enzyme preparations after treatment with the drug whereas the effect of most of the thiobarbiturates cannot. The addition of excess magnesium does not reverse the action of either the barbiturates or dinitrophenol. Dinitrophenol, thiopental, and pentobarbital are shown to inhibit the oxidation of octanoate by liver mitochondria.