Effect of 4-dimethylaminomethyl-1-(3-hydroxyphenyl)-1-nonen-3-one hydrochloride and related compounds on respiration in rat liver mitochondria.

4-Dimethylaminomethyl-1-(3-hydroxyphenyl)-1-nonen 3-one hydrochloride (II) was shown to stimulate respiration in rat liver mitochondria at levels of 2.5 mumoles or less; but at levels higher than 5.0 mumoles, respiration was inhibited when succinate and 3-hydroxybutyrate were the substrates. Compound II caused inhibition of respiration in the presence of glutamate over the dose range studied. The stimulating effect of II was attributed to its functioning as an uncoupling agent. Its inhibiting properties were considered to be due to its behaving like antimycin A in blocking transport of electrons between cytochromes b and c1. The effect of II on respiration in mitochondria varied with the pH of the medium. A conjugated styryl ketone, which contained a nuclear hydroxy function and was structurally related to II, also stimulated respiration at low doses while inhibiting respiration at higher concentrations. Etherification of the hydroxy group led to compounds in which only stimulation of respiration was noted.