Barbiturates and oxidative phosphorylation

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Abstract
The oxybarbiturates pheno-barbital, Amytal (amobarbital) and hexobarbital inhibit but do not uncouple oxidative phosphorylation of liver mitochondria with pyruvate as substrate. The thiobarbiturates thiopental, Baytenal (sodium 5-allyl-5-isobutyl-thiobarbiturate) and Kemithal (thialbarbital) inhibit and, to a certain extent, uncouple oxidative phosphorylation. The uncoupling appears to be correlated with their ability to activate mitochondrial adenosine triphosphatase. Results with brain mitochondria are in qualitative agreement with those with liver mitochondria but owing to the instability of the preparation the interpretation of these results is uncertain. The oxybarbiturates inhibited oxygen uptake stimulated by 2,4-dinitrophenol. In contrast adenosine triphosphatase activity stimulated by 2,4-dinitrophenol was not inhibited. The thiobarbiturates inhibit the oxygen uptake and, to a lesser extent, the adenosine triphosphatase. Neither Amytal nor Kemithal inhibits oxidation in the presence of succinate. The interpretation of these results in the light of current views of the respiratory chain is discussed.