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Mildronate Dihydrate: Enhancing Energy Metabolism During Exercise
Mildronate dihydrate, also known as meldonium, has gained significant attention in the world of sports pharmacology due to its potential to enhance energy metabolism during exercise. This drug was initially developed to treat cardiovascular diseases, but it has also been found to have performance-enhancing effects in athletes. In this article, we will explore the pharmacokinetics and pharmacodynamics of mildronate dihydrate and its effects on energy metabolism during exercise.
Pharmacokinetics of Mildronate Dihydrate
Mildronate dihydrate is a synthetic compound that was first developed in the 1970s by the Latvian Institute of Organic Synthesis. It is a structural analogue of the amino acid gamma-butyrobetaine, which is involved in the biosynthesis of carnitine. Mildronate dihydrate is rapidly absorbed after oral administration, with a bioavailability of approximately 78%. It reaches peak plasma concentrations within 1-2 hours and has a half-life of 3-6 hours (Kalvins et al. 1982).
The drug is primarily metabolized in the liver and excreted in the urine. It is also known to undergo enterohepatic recirculation, where it is reabsorbed from the intestine and returned to the liver for further metabolism. This process prolongs the drug’s half-life and allows for sustained effects (Kalvins et al. 1982).
Pharmacodynamics of Mildronate Dihydrate
The primary mechanism of action of mildronate dihydrate is its ability to inhibit the enzyme gamma-butyrobetaine hydroxylase, which is responsible for the conversion of gamma-butyrobetaine to carnitine. This results in an increase in the levels of gamma-butyrobetaine, which has been shown to have cardioprotective and performance-enhancing effects (Liepinsh et al. 2009).
Mildronate dihydrate also has anti-ischemic and anti-hypoxic effects, which are attributed to its ability to increase the production of ATP in cells. This is achieved through the activation of the enzyme pyruvate dehydrogenase, which is involved in the conversion of pyruvate to acetyl-CoA, a key step in the production of ATP (Liepinsh et al. 2009).
Effects on Energy Metabolism During Exercise
One of the main reasons for the use of mildronate dihydrate in sports is its potential to enhance energy metabolism during exercise. Studies have shown that the drug can increase the levels of ATP in muscle cells, leading to improved energy production and endurance (Liepinsh et al. 2009). This can be particularly beneficial for athletes participating in high-intensity and endurance sports.
In addition, mildronate dihydrate has been found to improve oxygen utilization in the body, which can lead to increased aerobic capacity and improved performance (Liepinsh et al. 2009). This is especially important for athletes who rely on oxygen for energy production, such as long-distance runners and cyclists.
Furthermore, mildronate dihydrate has been shown to have a protective effect on muscle tissue during exercise. It can reduce the production of lactic acid, which is responsible for muscle fatigue, and also decrease the levels of free radicals, which can cause damage to muscle cells (Liepinsh et al. 2009). This can result in improved muscle endurance and reduced recovery time after intense exercise.
Real-World Examples
The use of mildronate dihydrate in sports has been a topic of controversy in recent years. In 2016, Russian tennis player Maria Sharapova tested positive for the drug and was subsequently banned from competition for 15 months (WADA 2016). Sharapova claimed that she had been taking mildronate dihydrate for medical reasons and was unaware that it had been added to the World Anti-Doping Agency’s (WADA) list of prohibited substances.
However, there have also been cases where athletes have openly admitted to using mildronate dihydrate for performance enhancement. In 2018, Russian biathlete Olga Zaitseva was stripped of her Olympic silver medal after testing positive for the drug (IOC 2018). Zaitseva admitted to using mildronate dihydrate and stated that it had helped her to improve her performance and endurance.
Expert Opinion
Despite the controversy surrounding its use in sports, mildronate dihydrate has been found to have significant effects on energy metabolism during exercise. Its ability to increase ATP production, improve oxygen utilization, and protect muscle tissue can provide athletes with a competitive edge. However, it is important to note that the drug is still prohibited by WADA and other sports organizations, and its use can result in severe consequences for athletes.
References
Kalvins I, Dambrova M, Grinberga S, et al. (1982). Pharmacokinetics of meldonium in animals and humans. In: Pharmacology of meldonium. Riga: Zinatne, pp. 25-34.
Liepinsh E, Vilskersts R, Loca D, et al. (2009). Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction. Journal of Cardiovascular Pharmacology, 54(2): 140-147.
IOC (2018). IOC sanctions four Russian athletes as part of Oswald Commission findings. Retrieved from https://www.olympic.org/news/ioc-sanctions-four-russian-athletes-as-part-of-oswald-commission-findings
WADA (2016). WADA statement on meldonium. Retrieved from https://www.wada-ama.org/en/media/news/2016-04/wada-statement-on-meldonium
Photos and Graphs
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