Mitochondria represent a possible drug target with unexplored therapeutic and toxicological potential. The possibility was suggested that antidepressants, mood stabilizers and other drugs may show some therapeutic and/or toxic effects through their action on mitochondrial functions. There are no sufficient data about the effect of these drugs on mitochondrial respiration in the brain. We investigated the in vitro effects of amitriptyline, fluoxetine, tianeptine, ketamine, lithium, valproate, olanzapine, chlorpromazine and propranolol on mitochondrial respiration in crude mitochondrial fractions of pig brains. Respiration was energized using substrates of complex I or complex II and dose dependent drug-induced changes in mitochondrial respiratory rate were measured by high-resolution respirometry. Antidepressants, but not mood stabilizers, ketamine and propranolol were found to inhibit mitochondrial respiratory rate. The effective dose of antidepressants reaching half the maximal respiratory rate was in the range of 0.07-0.46 mmol/L. Partial inhibition was found for all inhibitors. Differences between individual drugs with similar physicochemical properties indicate selectivity of drug-induced changes in mitochondrial respiratory rate. Our findings suggest that mood stabilizers do not interfere with brain mitochondrial respiration, whereas direct mitochondrial targeting is involved in mechanisms of action of pharmacologically different antidepressants.

Department of Psychiatry Charles University Prague and General University Hospital Prague Ke Karlovu 11 120 00 Prague Czech Republic

Citace poskytuje Crossref.org

Different Effects of SSRIs, Bupropion, and Trazodone on Mitochondrial Functions and Monoamine Oxidase Isoform Activity

Agomelatine, Ketamine and Vortioxetine Attenuate Energy Cell Metabolism-In Vitro Study

Assessment of the Effects of Drugs on Mitochondrial Respiration

Effects of Novel Tacrine Derivatives on Mitochondrial Energy Metabolism and Monoamine Oxidase Activity-In Vitro Study

In vitro effects of antidepressants and mood-stabilizing drugs on cell energy metabolism

In vitro effects of antipsychotics on mitochondrial respiration

Disturbances of mitochondrial parameters to distinguish patients with depressive episode of bipolar disorder and major depressive disorder

In Vitro Effects of Cognitives and Nootropics on Mitochondrial Respiration and Monoamine Oxidase Activity

Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation