Psychotropic and neurological medication effects on mitochondrial complex I and IV in rodent models

Mitochondrial complex I (NADH-dehydrogenase) and complex IV (cytochrome-c-oxidase) are reported to be affected by drugs used to treat psychiatric or neurodegenerative diseases, including antidepressants, antipsychotics, anxiolytics, mood stabilizers, stimulants, antidementia, and antiparkinsonian drugs. We conducted meta-analyses examining the effects of each drug category on complex I and IV. The electronic databases Pubmed, EMBASE, CENTRAL, and Google Scholar were searched for studies published between 1970 and 2018. Of 3105 screened studies, 68 articles covering 53 drugs were included in the meta-analyses. All studies assessed complex I and IV in rodent brain at the level of enzyme activity. Results revealed that selected antidepressants increase or decrease complex I and IV, antipsychotics and stimulants decrease complex I but increase complex IV, whereas anxiolytics, mood stabilizers, antidementia, and antiparkinsonian drugs preserve or even enhance both complex I and IV. Potential contributions to the drug effects were found to be related to the drugs' neurotransmitter receptor profiles with adrenergic (α1B), dopaminergic (D1/2), glutaminergic (NMDA1,3), histaminergic (H1), muscarinic (M1,3), opioid (OP1-3), serotonergic (5-HT_2A, 5-HT_2C, 5-HT_3A) and sigma (σ1) receptors having the greatest effects. The findings are discussed in relation to pharmacological mechanisms of action that might have relevance for clinical and research applications.