Effect of cloxazepine on mitochondria

Cloxazepine is a neuroleptic drug synthesized at the Research Chemical Pharmaceutical Institute, Sofia. Chemically it represents 2-chloro-11 (4-methyl-1-piperazinyl)-dibenz (1,4)-oxazepine succinate. The effect of cloxazepine on respiration and phosphorylation of isolated brain mitochondria as well as on the swelling of rat liver mitochondria was examined. It has been demonstrated that the drug is a very poor inhibitor of the respiratory chain, acting mainly on its substrate end. At concentration of 0.5 mM it causes a 50 per cent inhibition of the soluble mitochondrial ATPase. It has a marked membrane action: it uncouples oxidative phosphorylation and causes swelling of the mitochondria. The results show that pharmacological action of cloxazepine is not connected with influence on the energy metabolism but with membrane action of the drug.