ACTION OF CHLORPROMAZINE AND IMIPRAMINE ON RAT-BRAIN MITOCHONDRIA

1. 1. Effects of chlorpormazine, imipramine as well as meprobamate on rat brain mitochondria were investigated in vitro. 2. 2. Chlorpromazine and imipramine uncoupled oxidative phosphorylation and inhibited mitochondrial respiration at state 3. I50 for chlorpromazine and imipramine were 2.4 × 10-4 and 7.5 × 10-4 M respectively. 3. 3. This inhibition was enhanced by classical uncoupler of oxidative phosphorylation (2,4-dinitrophenol). 4. 4. Meprobamate at reasonable concentration was without effect on mitochondrial functions. 5. 5. Chlorpromazine and imipramine induced also rise of rat brain mitochondrial membrane passive permeability to K+ cations. 6. 6. It is concluded that loss of K+ from mitochondria as well as membrane deenergization are responsible for matrix dehydratation and inhibition observed. © 1979.