Meldonium (INN; trade name Mildronate, among others) is a pharmaceutical developed in 1970 by Ivars Kalviņš at the USSR Latvia Institute of Organic Synthesis.

[1] Meldonium is prescribed for cardiovascular, neurological, and metabolic conditions due to its anti-ischaemic and cardioprotective effects, achieved by inhibiting β-oxidation and activating glycolysis.

[5][6] In some countries, particularly in Eastern Europe, meldonium is used to treat problems with brain circulation and has been reported to elevate mood and improve motor symptoms, dizziness, and nausea.

[7] The mechanism of action of meldonium is to act as a fatty acid oxidation inhibitor, presumably by inhibiting enzymes in the carnitine biosynthesis pathway such as γ-butyrobetaine hydroxylase.

Long chain FA are first activated via esterification with coenzyme A to produce a fatty acid-coA complex which can then cross the external mitochondrial border.

The final effect is a decreased risk of mitochondrial injury from fatty acid oxidation and a reduction of the production of acylcarnitines, which has been implicated in the development of insulin resistance.

[24] Meldonium was added to the World Anti-Doping Agency (WADA) list of banned substances effective 1 January 2016 because of evidence of its use by athletes with the intention of enhancing performance.

On 7 March 2016, former world number one tennis player Maria Sharapova announced that she had failed a drug test in Australia due to the detection of meldonium.

[34][35][36] Earlier the same year (March 7), Russian ice dancer Ekaterina Bobrova announced that she had also tested positive for meldonium at the 2016 European Figure Skating Championships.

This was discovered just a week prior to his mandatory title match against World Boxing Council (WBC) Heavyweight Champion, Deontay Wilder.

[81] On 25 March 2016 the Fédération Internationale de Sambo confirmed that four wrestlers under their governance (two from Russia and two from other countries) had recorded positive tests for the drug.

[82] A December 2015 study in the journal Drug Testing and Analysis argued that meldonium "demonstrates an increase in endurance performance of athletes, improved rehabilitation after exercise, protection against stress, and enhanced activation of central nervous system (CNS) functions".

"Meldonium cannot improve athletic performance, but it can stop tissue damage in the case of ischemia", the lack of blood flow to an area of the body.

[88][89] Liene Kozlovska, the former head of the anti-doping department of the Latvian sports medicine center, rejected claims that the ban is in violation of athletes' rights, saying that meldonium is dangerous in high doses, and should only be used under medical supervision to treat genuine health conditions.

[90] Forbes reported that anesthesiology professor Michael Joyner, at the Mayo Clinic in Rochester, Minnesota, who studies how humans respond to physical and mental stress during exercise and other activities, told them that "Evidence is lacking for many compounds believed to enhance athletic performance.

I would be shocked if this stuff [meldonium] had an effect greater than caffeine or creatine (a natural substance that, when taken as a supplement, is thought to enhance muscle mass).

[92] Don Catlin, a long-time anti-doping expert and the scientific director of the Banned Substances Control Group (BSCG) said "There's really no evidence that there's any performance enhancement from meldonium – Zero percent".

[93] Meldonium, which is not approved by the FDA in the United States, is registered and prescribed in Latvia, Russia, Ukraine, Georgia, Kazakhstan, Azerbaijan, Belarus, Uzbekistan, Moldova, Lithuania, Albania, and Kyrgyzstan.

[83][94] Meldonium is manufactured by Grindeks, a Latvian pharmaceutical company, with offices in thirteen Eastern European countries[95] as a treatment for heart conditions.