What is trimetazidine and why is it banned at the Olympics?

Trimetazidine (TMZ) is a common name for 1- (2,3,4-trimethoxybenzyl) piperazine. The chemical acts as a vasodilator and was discovered more than 50 years ago. In Europe and Russia, where it is commonly prescribed, TMZ is taken as tablets or sustained-release tablets to treat angina, as well as dizziness, tinnitus and some visual disturbances. The U.S. Food and Drug Administration has not approved TMZ for use in the United States.

Inside the body, TMZ inhibits fatty acid oxidation by shifting metabolism toward glucose oxidation. This means that ATP, an energy molecule in cells, can be made more efficient in a low-oxygen environment. Although trimetazidine is metabolized in the body, it does not stay too long and most of the drug is excreted in the urine unchanged. In young healthy adults, the half-life of TMZ is approximately 8 hours; in elderly patients it increases to 12 hours, says Justin Brawer, a forensic toxicologist with the North Carolina Office of Chief Medical Officer

About 700 sports organizations have signed the World Anti-Doping Code, which is administered by the World Anti-Doping Agency, WADA. Since 2014, WADA has classified TMZ as a banned 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 can give athletes an advantage in competitions by reducing their fatigue at height and increasing their cardiovascular fitness (Biomed. Pharmacother. 2019, DOI: 10.1016 / j.biopha.2019.109003).

Because TMZ passes easily into the urine, WADA labs typically test athletes ’urine samples when searching for a drug. When WADA first banned TMZ, Mario Tavis and colleagues at the German Sports University in Cologne showed that mass spectrometry could detect TMZ and several of its metabolites in urine samples (Drug test. Anal. 2014, DOI: 10.1002 / dta.1680). Tavis told C&EN in an email that today TMZ is most often found using tandem liquid spectrometry liquid chromatography. When German researchers tested historical urine samples taken from athletes before TMZ was banned, they found that TMZ was most commonly found in athletes engaged in endurance and strength sports.

False positive results for TMZ may be caused by migraine treatment with lomerisin, which is not prohibited by WADA because the body produces some amount of TMZ when it breaks down lomerisin. To distinguish the source of TMZLaboratories use their tools to detect unique metabolites of lomerisin, such as N-dealkylated lomerisin, which is not formed by TMZ degradation.