Trimetazidine, an Anti-Ischemic Drug, Reduces the Antielectroshock Effects of Certain First-Generation Antiepileptic Drugs

Abstract

Trimetazidine (TMZ), an anti-ischemic drug for improving cellular metabolism, is mostly administered to patients with poorly controlled ischemic heart disease (IHD). Since IHD is considered the most frequent causative factor of cardiac arrhythmias, and these often coexist with seizure disorders, we decided to investigate the effect of TMZ in the electroconvulsive threshold test (ECT) and its influence on the action of four first-generation antiepileptic drugs in the maximal electroshock test (MES) in mice. The TMZ (up to 120 mg/kg) did not affect the ECT, but applied at doses of 20–120 mg/kg it decreased the antielectroshock action of phenobarbital. The TMZ (50–120 mg/kg) reduced the effect of phenytoin, and, when administered at a dose of 120 mg/kg, it diminished the action of carbamazepine. All of these revealed interactions seem to be pharmacodynamic, since the TMZ did not affect the brain levels of antiepileptic drugs. Furthermore, the combination of TMZ with valproate (but not with other antiepileptic drugs) significantly impaired motor coordination, evaluated using the chimney test. Long-term memory, assessed with a passive-avoidance task, was not affected by either the TMZ or its combinations with antiepileptic drugs. The obtained results suggest that TMZ may not be beneficial as an add-on therapy in patients with IHD and epilepsy.

Modification of Preservative Fluids with Antioxidants in Terms of Their Efficacy in Liver Protection before Transplantation

“…Reduces the excessive release of ROS and improves mitochondrial function. It influences the proper functioning of the sodium-potassium pump and cell homeostasis [107]. Ben et al [44] studied the efficacy of TMZ in an isolated Zücker rat liver model.…”

Role of Trimetazidine in Ameliorating Endothelial Dysfunction: A Review

“…Additionally, trimetazidine may interact with medications prescribed for other coexisting conditions in patients with endothelial dysfunction, potentially compromising its efficacy or increasing the likelihood of adverse effects. Recent findings suggest that trimetazidine can attenuate the effects of antiepileptic drugs such as phenytoin and carbamazepine without affecting their brain levels [ 95 ]. Therefore, healthcare providers must exercise caution and meticulously assess potential drug interactions when prescribing trimetazidine to patients with endothelial dysfunction.…”

Rational Engineering of Mesorhizobium Imine Reductase for Improved Synthesis of N-Benzyl Cyclo-tertiary Amines

“…N-benzyl cyclo-tertiary amines are basic building blocks of many active pharmaceutical ingredients, such as donepezil [1] and trimetazidine [2] (Figure 1). Developing efficient pathways that allow for the synthesis of N-benzyl tertiary amines, especially starting from N-cyclic secondary amines, is an attractive route.…”