Effects of phenobarbital on activity of mitochondrial enzymes in peripheral blood lymphocytes and oxidative phosphorylation in liver mitochondria.

Treatment with phenobarbital (30 mg/kg) for 2 weeks increased succinate dehydrogenase activity in peripheral blood lymphocytes of male rats. In 38% phenobarbital-treated rats succinate-cytochrome c oxidoreductase activity was lower than in the control due to accumulation of cells exhibiting no enzyme activity; in 44% animals this parameter was higher than in the control. The rates of state 3 respiration (oxidation substrate succinate), phosphorylation, and uncoupled respiration in liver mitochondria (oxidation substrate glutamate/malate mixture) increased after 35-day treatment with phenobarbital. The respiratory control and ADP/O ratio for these substrates did not differ from the control.

The uncoupling effect of some psychotropic drugs on oxidative phosphorylation in rat liver mitochondria.

In the present study an attempt to detect influence of some psychotropic drugs on oxidative phosphorylation has been made. Relanium and melipramine were used in the experiments. They are among tranquilizer and antidepressant drug groups respectively. It was shown that both drugs increased the rate of oxygen consumption and displayed uncoupling properties. Mitochondrial respiration raised up slowly after drug addition in the presence of succinate or beta-oxybutyrate as oxidized substrates. If concentration of relanium and melipramine exceeded 1.2 and 0.8 mM respectively the rate of oxygen consumption began to decrease. There was a small reply on addition of ADP in the presence of drugs. At the same time relanium and melipramine decreased respiration rate if they were added at the state 3. It was shown that the drugs increased conductivity of bimolecular phospholipid membranes.