Chlorphentermine-induced biochemical alterations in mitochondrial membranes

The effects of chlorphentermine (CP) on bioenergetics and monoamine oxidase activity in rat liver mitochondria were examined. Oxidation rates of isocitrate, glutamate and succinate were investigated in the presence of CP (0.5-5.0 mM). In the presence of low concentrations (0.5-2.0 mM) CP decreased respiratory control ratio and ADP/O ratio, and stimulated state 4 respiration. State 3 respiration and uncoupled state were unaffected. The same pattern of changes was found after in vivo CP treatment for 1 or 2 weeks (30 mg/kg i.p., 5 days/week). CP also increased respiration in state 3 that had been inhibited previously by oligomycin. These data indicate that CP functions as an uncoupler of oxidative phosphorylation. In the presence of higher concentrations of CP (3.0-5.0 mM), respiration in states 4, 3 and in uncoupled state, as well as respiratory control ratio and ADP/O, were decreased. Oxidation of norepinephrine, serotonin, tyramine and dopamine by monoamine oxidase, an enzyme marker of the outer mitochondrial membrane, was inhibited in the presence of 0.05 to 0.5 mM CP. Tryptamine and benzylamine oxidation was unaffected. A kinetic study of serotonin oxidation in the absence and presence of CP (0.05-0.25 mM) indicated that both the Vmax and Km were affected. This drug is an inhibitor of liver mitochondrial monoamine oxidase with mixed-type inhibition. These combined data show that CP affects biochemical processes in both inner and outer mitochondrial membranes.