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Forensic Science

What is trimetazidine and why is it banned in Olympic competition?

Russian skater Kamila Valieva tested positive for the angina medication, which causes metabolic shifts

by Laura Howes
February 17, 2022


The chemical structure of trimetazidine also known as TMZ.

On Feb. 11, 2022, the International Testing Agency, which is responsible for monitoring doping at the Winter Olympics in Bejing, confirmed that a sample from the Russian figure skater Kamila Valieva contained the banned substance trimetazidine.

Trimetazidine (TMZ) is the generic name for 1-(2,3,4-trimethoxybenzyl)piperazine. The chemical acts as a vasodilator and was discovered over 50 years ago. In Europe and Russia where it is commonly prescribed, TMZ is taken as a pill or in delayed-release tablets to treat angina as well as vertigo, tinnitus, and certain visual disturbances. The US Food and Drug Administration has not approved TMZ for use in the US.

Inside the body, TMZ inhibits fatty acid oxidation, shifting metabolism towards glucose oxidation. That means that ATP, the energy molecule in cells, can be made more efficiently in low-oxygen environments. Though trimetazidine is metabolized by the body, it doesn’t stick around too long, and most of the drug comes out in urine unaltered. In young, healthy adults, the half-life of TMZ is approximately 8 h; it increases to 12 h in elderly patients, says Justin Brower, a forensic toxicologist at the North Carolina Office of the Chief Medical Examiner

Around 700 sports organizations have signed the world anti-doping code, which is managed by the World Anti-Doping Agency, WADA. Since 2014, WADA has classed TMZ as a prohibited substance. The drug is currently listed as a “metabolic modulator” and WADA prohibits athletes from using the drug in or out of competition. A shift in how the body uses energy could give athletes an edge in competitions by lessening their altitude fatigue and increasing their cardiovascular fitness (Biomed. Pharmacother. 2019, DOI: 10.1016/j.biopha.2019.109003).

Because TMZ passes easily into urine, WADA laboratories usually test athletes’ urine samples when looking for the drug. Back when WADA first banned TMZ, Mario Thevis and colleagues at the German Sport University in Cologne showed that mass spectrometry techniques can detect TMZ and several of its metabolites in urine samples (Drug Test. Anal. 2014, DOI: 10.1002/dta.1680). Thevis told C&EN in an email that today, TMZ is most commonly found using liquid chromatography tandem mass spectrometry. When the German researchers tested historical urine samples taken from athletes before TMZ was banned, they found that TMZ was most often detected in athletes involved in endurance and strength sports.

False positive results for TMZ could be caused by the migraine treatment lomerizine, which isn’t banned by WADA, because the body makes some TMZ when it breaks down lomerizine. To distinguish the source of TMZ, laboratories use their instruments to detect unique metabolites of lomerizine, like N-dealkylated lomerizine, which is not produced by the breakdown of TMZ.



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