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Aldridge and Parker (1960) using suspensions of liver mitochondria demonstrated with oxybarbiturates an inhibition of respiration without uncoupling oxidative phosphorylation. This was in contrast to the views expressed by Brody and Bain (1954) who suggested that the mode of action of the barbiturates on the C .N .S . was mediated by an uncoupling of oxidative phosphorylation. Aldridge and Parker further showed that the use of succinate as substrate for the mitochondrial suspension abolished the inhibition of respiration caused by the oxybarbiturate and suggested therefore that the site of action of the oxybarbiturate was at some stage before the entry of succinate into the oxidative chain. Succinate is known to enter the oxidative site at a point after the pyridine nucleotide stage and hence the site of action of barbiturate was proposed to be at the oxidation of pyridine nucleotide.

Research Topic: On the Mode of Action of Barbituates In Vivo