Effects of butalamine on oxydative phosphorylations in the rat liver

The effect of 3-phenyl-4-dibutylaminoethyl-5-inimino-1,2,4-oxadiazole (butalamine) was investigated in vivo and in vitro on oxydophosphorylation of mitochondria isolated from rat liver. In vitro with succinate and glutamate-malate as oxydable substrates, butalamine stimulates respiration at lower concentrations (100% at 3 X 10(-4) M for succinate and 40% at 4 X 10(-4) M for glutamate-malate) and inhibits it at higher ones (50% at 1 mM). Butalamine inhibits State 3 respiration and decreases ADP/O. Data on respiration blocked by rutamycine and on the effects of DNP, show that butalamine affects oxydophosphorylation in vitro, probably before DNP reactions are involved. In contrast to DNP, butalamine is an uncompetitive inhibitor when succinate is used as substrate in State 3. The potent lipophilic properties of butalamine should be responsible for these unspecific effects. In vivo, at a dosage of 50 mg/kg p.o. over 8 days, no alteration of State 3, State 4, ADP/O and respiratory control ratio (RC) was found.