Abstract
Metabolism of diethylaminoethyl 2,2-diphenylvalerate HCl (SKF 525-A) or its primary amine analogue causes formation of a stable oxygenated complex of ferrous P-450. The complex is also generated in vivo and survives preparation of liver microsomes. Formation of the complex requires active metabolism of either SKF 525-A or the N-dealkylated primary amine, SKF 26754A. This new species has an absorption maximum at 455 nm. Oxidation of the hemoprotein with potassium ferricyanide causes loss of the absorption band, but subsequent reduction and oxygenation of the medium restore it. This new complex is believed to be responsible for the observed noncompetitive inhibition of drug metabolism in vitro by SKF 525-A.
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