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Effect of cloxazepine on mitochondria
Acta Physiologica Et Pharmacologica Bulgarica
|January 1, 1981
Summary
Cloxazepine, a neuroleptic drug, primarily affects cell membranes rather than energy metabolism. Its action involves uncoupling oxidative phosphorylation and causing mitochondrial swelling, not inhibiting the respiratory chain.
Area of Science:
- Pharmacology
- Biochemistry
- Mitochondrial research
Background:
- Cloxazepine is a neuroleptic agent developed at the Research Chemical Pharmaceutical Institute, Sofia.
- Its chemical structure is 2-chloro-11 (4-methyl-1-piperazinyl)-dibenz (1,4)-oxazepine succinate.
Purpose of the Study:
- To investigate the effects of cloxazepine on mitochondrial respiration and phosphorylation.
- To examine the impact of cloxazepine on the swelling of isolated rat liver mitochondria.
Main Methods:
- Assessing the inhibition of the respiratory chain in isolated brain mitochondria.
- Measuring the effect on soluble mitochondrial ATPase activity.
- Observing mitochondrial swelling and uncoupling of oxidative phosphorylation in rat liver mitochondria.
Main Results:
- Cloxazepine is a weak inhibitor of the respiratory chain, primarily affecting its substrate end.
- It inhibits soluble mitochondrial ATPase by 50% at a 0.5 mM concentration.
- The drug exhibits significant membrane action, uncoupling oxidative phosphorylation and inducing mitochondrial swelling.
Conclusions:
- The pharmacological action of cloxazepine is attributed to its membrane effects.
- Its primary mechanism of action is not related to influencing energy metabolism directly.
- Cloxazepine's interaction with mitochondrial membranes is key to its neuroleptic effects.