Antipsychotic‐Like Effect of Trimetazidine in a Rodent Model

Abstract

Trimetazidine (TMZ) has been used as an anti-ischemic agent for angina pectoris, chorioretinal disturbances, and vertigo. Also, it can induce extrapyramidal type adverse reaction such as parkinsonism, gait disorder, and tremor via blockade of D2 receptors. In the present study, we evaluated the effect of TMZ on novelty-induced rearing behavior and apomorphine-induced stereotypy behavior in male rats. Four groups of rat (n = 7) were administrated with TMZ (10 and 20 mg/kg, i.p.), chlorpromazine (1 mg/kg, i.p.), or isotonic saline. One hour later, apomorphine (2 mg/kg, s.c.) was administrated to each rat. Our results showed that both doses of TMZ significantly decreased the rearing behavior in rats, whereas the decrease with chlorpromazine was higher. TMZ also decreased the stereotypy scores in a dose-dependent manner. We concluded that TMZ has beneficial effects on rearing behavior and stereotypy, which are accepted to be indicators of antipsychotic effect. Taken together, with its antioxidative and cytoprotective properties, TMZ is worthy of being investigated for its anti-psychotic effects as a primary or an adjunctive drug.

Central Beneficial Effects of Trimetazidine on Psychomotor Performance in Normal Healthy Volunteers

“…demonstrated modulation of rearing and stereotype behavior due to trimetazidine therapy mediated by mesolimbic dopaminergic effects. [ 12 ]…”

The Impact of Trimetazidine on Disease Severity and Quality of Life in Parkinson’s Disease

“…Drugs owning a piperazine core can process strong postsynaptic inhibition of dopamine receptors, including dopamine D2 receptors 10 , which are present in many brain structures such as the striatum having a substantial role in regulation of movements. The potential antipsychotic-like effect of TMZ described in a rodent model may also support the hypothesis that TMZ can cross the blood-brain barrier and interact with dopamine receptors in the central nervous system 15 .Based on available findings, the European Medicines Agency (EMA) made a recommendation for the more careful use of TMZ in certain groups of patients and against the application of the drug for the treatment of patients with PD in 2012 16 . However, some recent data show that this recommendation is not followed strictly enough since a not negligible part of TMZ users is still patients with movement disorders diagnosed prior to the prescription of the drug 13 .Although motor symptoms of reversible TMZ-induced parkinsonism have been considered to be mild by previous descriptions 5,7,9,11 , they can have a serious impact on the health-related quality of life (HRQoL) 5 .…”

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

“…Among other mechanisms of action, TMZ has been reported to block dopamine D 2 receptors [ 7 ] and increase the serum and platelet levels of serotonin [ 18 ]. Increased brain concentration of serotonin can also modulate seizure processes.…”

“…On the other hand, it has been reported that inducible loss of D 2 receptors causes significant motor impairment in mice [ 37 , 38 ]. Bearing in mind the fact that TMZ blocks dopaminergic D 2 receptors [ 7 ], one can assume that the addition of the two mechanisms can trigger motor impairment in animals treated concomitantly with valproate and TMZ. Nevertheless, this hypothesis does not seem to be reliable in light of results for phenobarbital, a potent agonist of the barbiturate site within the GABA-related complex.…”

“…In general, TMZ is very well tolerated; however, due to the blockade of D 2 receptors, it can induce extrapyramidal motor disturbances, gait disorders, and tremors. Therefore, this drug is contraindicated in patients with Parkinson’s disease and Parkinsonian symptoms [ 7 ]. Under experimental conditions, TMZ has demonstrated gastroprotective, hepatoprotective, anti-inflammatory, antinociceptive, and antiapoptotic effects [ 8 , 9 ].…”