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Bio pharmaceutical studies on neuroleptic butyrophenones part 1 effects of some butyrophenones on the oxygen uptake by liver slices and homogenates and on the function of liver mitochondria



Bio pharmaceutical studies on neuroleptic butyrophenones part 1 effects of some butyrophenones on the oxygen uptake by liver slices and homogenates and on the function of liver mitochondria



Yakugaku Zasshi 97(4): 416-421



All neuroleptic butyrophenones examined and chlorpromazine at relatively high concentrations of 10-4-10-3 M decreased the O2 uptake by rat liver slices. At low concentrations of 10-5-10-4 M, butyrophenones and chlorpromazine strongly stimulated the O2 uptake by rat liver homogenates when glucose, pyruvate and succinate were used as substrates, but at a high concentration of 10-3 M, clofluperol, moperone and chlorpromazine decreased the O2 uptake, while trifluperidol and haloperidol still stimulated the O2 uptake by liver homogenates. Clofluperol, the most potent neuroleptics among 4 kinds of butyrophenones used, at concentrations of 5 .times. 10-5-10-4 M stimulated the state 4 respiration induced by succinate, .beta.-hydroxybutyrate and glutamate, and inhibited the oxidative phosphorylation in rat liver mitochondria. It also activated latent ATPase of liver mitochondria similar to the typical uncoupler 2,4-dinitrophenol. At a higher concentration above 2.5 .times. 10-4M, it caused aggregation of mitochondria and impaired the function of mitochondria. Neuroleptic butyrophenones may also interact with biological membranes in a similar manner as phenothiazines.

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