Fig. 2: Trimetazidine is a selective inhibitor of 3-ketoacyl-CoA thiolase.

Hence trimetazidine modulates mitochondrial energy production by inhibiting fatty acid oxidation to engage efficient glucose oxidation, which increases adenosine triphosphate (ATP) conversion compared to oxygen consumed. Trimetazidine also increases pyruvate dehydrogenase activity to decrease lactate accumulation. These effects ultimately reduces intracellular calcium ion accumulation and reactive oxygen species (ROS) to reduce apoptosis, inflammation and oxidative stress indicated by reduced level of biomarkers such as tumor necrosis factor alpha (TNF-α) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2. Trimetazidine has also been shown to increase antioxidant activity measured by increased glutathione, glutathione peroxidase, superoxide dismutase (SOD), and catalase. Taken together, accumulating preclinical and clinical evidence of trimetazidine’s regulation of mitochondrial function, anti-inflammatory and antioxidant properties strongly support its potential efficacy to reduce bipolar depression. Figure created with Biorender.com.