Butyrophenone系薬物に関する生物薬剤学的研究(第1報)肝組織呼吸および肝ミトコンドリアの機能におよぼす影響

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All neuroleptic butyrophenones examined and chlorpromazine at relatively high concentrations of 10^<-4> to 10^<-3>M decreased the oxygen uptake by rat liver slices. At low concentrations of 10^<-5> to 10^<-4>M, butyrophenones and chlorpromazine strongly stimulated the oxygen 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 oxygen uptake, while trifluperidol and haloperidol still stimulated the oxygen uptake by liver homogenates. Clofluperol, the most potent neuroleptics among four kinds of butyrophenones used, at concentrations of 5×10^<-5> to 10^<-4>M stimulated the state 4 respiration induced by succinate, β-hydroxybutyrate, and glutamate, and inhibited the oxidative phosphorylation in rat liver mitochondria. It also activated latent ATPase of liver mitochondria as same as the typical uncoupler such as 2,4-dinitrophenol. On the other hand, at a higher concent ration above 2.5×10^<-4>M, it caused aggregation of mitochondria and impaired the function of mitochondria. These findings suggest that neuroleptic butyrophenones may also interact with biological membranes in a similar manner as phenothiazines.
公益社団法人日本薬学会の論文
1977-04-25