ANALGESICS AND ENZYMES OF THE CYTOCHROME CHAIN

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

Direct assay of enzyme activities by spectrophotometric methods demonstrated that DPN-cytochrome c reductase was the most sensitive of the cytochrome chain enzymes to the inhibitory action of morphine. In addition to the above inhibition, morphine and its derivatives having a free phenolic hydroxyl were shown to be active in catalyzing the transfer of electrons from reduced DPN to ferricytochrome c in the absence of enzyme. Potency as transferring agents was shown to be correlated with potency as inhibitors of DPN-cytochrome c reductase. Methadone had the most striking effect on cytochrome c oxidase stimulating at low concentrations and inhibiting at high concentrations. The l-isomer was more potent than the d-isomer. Meperidine apparently was most effective as an inhibitor of the dehydrogenase step in the malic dehydrogenase-DPN-cytochrome c reductase system having only a relatively small effect on cytochrome c oxidase.