Trimetazidine

Overview

Trimetazidine (IUPAC: 1-(2,3,4-trimethoxybenzyl)piperazine) is a drug used in the treatment of angina pectoris, a condition characterized by chest pain due to reduced blood flow to the heart. Developed and first marketed by Laboratoires Servier (France), it is described as the first cytoprotective anti-ischemic agent. Trimetazidine is an antianginal metabolic drug of the fatty acid oxidation inhibitor class; it shifts cardiac energy metabolism from fatty acid utilization toward glucose oxidation, thereby improving the efficiency of energy production in ischemic conditions.[1] WP

The drug has also become controversial as a performance-enhancing drug, with multiple doping scandals linked to its use at successive Olympic Games. WP

Uses, dosage and effects

Medical uses

Trimetazidine is prescribed primarily as a long-term treatment for angina pectoris. In some countries, including France, it has also been used for tinnitus and dizziness. The drug is typically administered twice daily. In 2012, the European Medicines Agency (EMA) completed a review of its benefits and risks and recommended restricting trimetazidine-containing medicines to use only as an add-on therapy for angina pectoris when first-line antianginal agents are insufficient or not tolerated.[2] WP

Controlled studies in patients with angina have shown that trimetazidine increases coronary flow reserve, delays the onset of exercise-induced ischemia, stabilizes blood pressure without significantly affecting heart rate, reduces the frequency of angina attacks, and decreases the need for symptomatic nitrate use.[3] WP

Trimetazidine has also been reported to improve left ventricular function in patients with coronary heart disease and diabetes.[4] WP

As of 2023, it is under investigation for the treatment of bipolar depression.[5] WP

Testing to determine if it can have a positive impact on patients suffering from ALS/MND is due to begin taking place in 2026.[6] WP

Risks and side effects

Adverse effects

Trimetazidine has been treated as a drug with a high safety and tolerability profile.[7] WP

Information is scarce about trimetazidine's effect on mortality, cardiovascular events, or quality of life. Long-term randomized, controlled trials comparing trimetazidine against standard antianginal agents using clinically important outcomes would be justifiable. A 2013 international multicentre retrospective cohort study has indeed shown that in patients with heart failure of different etiologies the addition of trimetazidine on conventional optimal therapy can improve mortality and morbidity.[7][8] WP

The EMA recommends that doctors no longer prescribe trimetazidine for the treatment of patients with tinnitus, vertigo, or disturbances in vision. The recent EMA evaluation also revealed rare cases (3.6/1,000,000 patient years) of parkinsonian (or extrapyramidal) symptoms (such as tremor, rigidity, akinesia, hypertonia), gait instability, restless leg syndrome, and other related movement disorders; most patients recovered within 4 months after treatment discontinuation, so doctors are advised not to prescribe the medicine either to patients with Parkinson disease, parkinsonian symptoms, tremors, restless leg syndrome, or other related movement disorders, or to patients with severe renal impairment. Parkinson's-like symptoms may increase the risk for falls, as it was observed in a case-control study.[2] WP

Pharmacology

Mechanism of action

Trimetazidine acts by modulating cellular energy metabolism, particularly the balance between fatty acid and glucose oxidation. WP

Under normal conditions, cells generate ATP (adenosine triphosphate), the primary energy currency, by oxidizing both fatty acids and glucose. However, during ischemia (reduced blood flow) or hypoxia (reduced oxygen supply), oxygen availability is limited, and fatty acid oxidation becomes inefficient, leading to reduced ATP production and impaired cellular function. WP

Trimetazidine selectively inhibits the mitochondrial enzyme long-chain 3-ketoacyl-CoA thiolase, a key catalyst in the beta-oxidation of fatty acids. Inhibition of this enzyme decreases fatty acid oxidation and shifts substrate utilization toward glucose oxidation. Because glucose oxidation consumes less oxygen per molecule of ATP produced than fatty acid oxidation, this metabolic shift improves the efficiency of ATP generation under oxygen-limited conditions.[9] WP

By preserving intracellular ATP levels, trimetazidine supports energy-dependent processes such as ionic pump activity and the maintenance of transmembrane sodium–potassium gradients. This stabilization of cellular homeostasis helps protect cardiac cells during ischemic stress.[10] WP

Chemistry

Formula

C14H22N2O3 PC

CAS number

5011-34-7 PC

Molar mass (g/mol)

266.34 PC

IUPAC name (computed by PubChem)

1-[(2,3,4-trimethoxyphenyl)methyl]piperazine PC

SMILES

COC1=C(C(=C(C=C1)CN2CCNCC2)OC)OC PC

InChIKey

UHWVSEOVJBQKBE-UHFFFAOYSA-N PC

PubChem CID

21109

IUPAC name

1-(2,3,4-trimethoxybenzyl)piperazine WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Trimetazidine
2. Journal / agency European Medicines Agency recommends restricting use of trimetazidine-containing medicines. 12 June 2012
3. Journal / agency Gupta R, Sawhney JP, Narain VS. Treatment of stable angina pectoris with trimetazidine modified release in Indian primary-care practice. American Journal of Cardiovascular Drugs. 2005. doi:10.2165/00129784-200505050-00005 · PMID 16156688
4. Journal / agency Marzilli M, Vinereanu D, Lopaschuk G, Chen Y, Dalal JJ, Danchin N, Etriby EL, Ferrari R, Gowdak LH, Lopatin Y, Milicic D, Rosano GM. Trimetazidine in cardiovascular medicine. International Journal of Cardiology. 2019. doi:10.1016/j.ijcard.2019.05.063 · PMID 31178223
5. Journal / agency Khanra S, Reddy P, Giménez-Palomo A, Park CH, Panizzutti B, McCallum M, Arumugham SS, Umesh S, Debnath M, Das B, Venkatasubramanian G, Ashton M, Turner A, Dean OM, Walder K, Vieta E, Yatham LN, Pacchiarotti I, Reddy YC, Goyal N, Kesavan M, Colomer L, Berk M, Kim JH. Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine. Molecular Psychiatry. August 2023. doi:10.1038/s41380-023-02134-8 · PMID 37386057 · PMC10618096
6. Other University of Queensland trial explores heart drug as potential ALS treatment. 2 September 2025
7. Journal / agency Ciapponi A, Pizarro R, Harrison J. Trimetazidine for stable angina. Cochrane Database Syst Rev. Oct 2005. doi:10.1002/14651858.CD003614.pub3 · PMID 16235330 · PMC6464521
8. Journal / agency Fragasso G, Rosano G, Baek SH, Sisakian H, Di Napoli P, Alberti L, Calori G, Kang SM, Sahakyan L, Sanosyan A, Vitale C, Marazzi G, Margonato A, Belardinelli R. Effect of partial fatty acid oxidation inhibition with trimetazidine on mortality and morbidity in heart failure: results from an international multicentre retrospective cohort study. International Journal of Cardiology. March 2013. doi:10.1016/j.ijcard.2012.09.123 · PMID 23073279
9. Journal / agency Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ. Res. March 2000. doi:10.1161/01.RES.86.5.580 · PMID 10720420
10. Journal / agency Stanley WC, Marzilli M. Metabolic therapy in the treatment of ischaemic heart disease: the pharmacology of trimetazidine. Fundam Clin Pharmacol. April 2003. doi:10.1046/j.1472-8206.2003.00154.x · PMID 12667223

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.