Comparative study: trimetazidine versus olanzapine on cognitive dysfunction and behavioral changes in ketamine-induced psychosis model in mice
Yosra M. Magdy, Sherif A. Kamar, Hoda A. Fansa, Sara Khedr, Amina Sedky
The Egyptian Journal of Neurology, Psychiatry and Neurosurgery April 29, 2025 DOI: 10.1186/s41983-025-00960-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice with ketamine-induced psychosis |
| Interventions | Trimetazidine Olanzapine Ketamine |
| Topics | Esketamine Ketamine |
| Key points | In mice with ketamine-induced psychosis, trimetazidine improved cognitive function, irisin, BDNF, and MDA levels, while olanzapine produced less cognitive improvement and reduced PGC1α and muscle grip. The authors propose trimetazidine works like exercise by increasing skeletal muscle mitochondrial PGC1α and plasma irisin, offering an alternative for schizophrenia patients with cognitive dysfunction who struggle with physical activity. |
Abstract
Mitochondrial dysfunction and oxidative stress may contribute to schizophrenia. Negative symptoms and cognitive dysfunction in individuals with schizophrenia are resistant to anti-psychotic medications, but physical exercise is an effective treatment. Exercise’s beneficial effects involve releasing irisin from skeletal muscle by activating mitochondrial peroxisome proliferator-activated receptor gamma co-activator 1-α (PGC1-α). “Irisin enhances cognitive function by boosting brain-derived neurotrophic factor (BDNF) and through its antioxidant properties.” Schizophrenia patients struggle to engage in physical activity due to dysfunction in their skeletal muscle mitochondria. Trimetazidine improves mitochondrial function and increases irisin release, offering an alternative to exercise for schizophrenics with cognitive dysfunction. The study compared trimetazidine to olanzapine in treating behavioral changes and cognitive dysfunction in mice with ketamine-induced psychosis. Researchers investigated the effects of trimetazidine on muscle power, mitochondrial function, plasma irisin level, and their correlation with hippocampal BDNF and MDA. Ketamine use in mice led to cognitive dysfunction, reduced BDNF, elevated MDA, decreased muscle grip, and irisin. Trimetazidine improved irisin and improved BDNF, MDA levels, and cognitive function. Trimetazidine works like exercise, leading to an increase in skeletal muscle mitochondrial PGC1α and plasma irisin. Olanzapine induced less improvement in cognitive function with a reduction in PGC1α and muscle grip.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |