Overview
Meldonium (3-(2,2,2-trimethylhydrazinium)propionate, brand name Mildronate) was developed by Latvian chemist Ivars Kalviņš in the 1970s. It is approved in Latvia, Russia, Ukraine, and several other post-Soviet states for ischemic heart disease, chronic heart failure, and cerebrovascular disorders.
Meldonium became internationally notorious in 2016 when WADA added it to the prohibited list after detecting widespread use among elite athletes (including tennis player Maria Sharapova). It is not approved by the FDA or EMA. Despite long clinical use in Eastern Europe, high-quality randomized trial evidence is limited.
Quick facts
- Mechanism
- Inhibits γ-butyrobetaine hydroxylase, reducing carnitine biosynthesis and shifting cardiac metabolism from fatty acid to glucose oxidation
- Primary use
- Ischemic heart disease and angina (approved in Eastern Europe); banned in sport
- Evidence
- moderate
- FDA
- Not approved
- Route
- Oral or IV
- Typical results
- Improvements in exercise tolerance in stable angina; controversial ergogenic effects
Chemical information
Meldonium (C₆H₁₄N₂O₂) is a metabolic compound with a molecular weight of 146.19 g/mol. Its structural characteristics underpin its biological activity in metabolic regulation and energy homeostasis.
How Meldonium works
Meldonium inhibits γ-butyrobetaine hydroxylase (BBOX), the final enzyme in carnitine biosynthesis, and also inhibits carnitine renal reabsorption. The resulting drop in tissue carnitine reduces long-chain fatty acid β-oxidation and shifts cardiac and skeletal muscle metabolism toward more oxygen-efficient glucose oxidation. This is theoretically protective in ischemic tissue where oxygen supply is limited.
By reducing accumulation of toxic fatty acid intermediates (acylcarnitines, long-chain acyl-CoA) during ischemia, meldonium limits mitochondrial damage and ATP depletion. It also upregulates eNOS, lowers blood pressure modestly, and increases NO-mediated vasodilation.
The ergogenic rationale in sport is enhanced recovery via reduced oxygen demand and improved endothelial function, though human performance data are limited and conflicting. Meldonium has a very long elimination tail and can be detected in urine months after discontinuation, which led to numerous athletes testing positive after the 2016 ban.
- BBOX inhibition: Blocks carnitine biosynthesis
- Metabolic shift: Glucose over fatty acid oxidation; oxygen sparing
- Endothelial effect: Upregulates eNOS and NO bioavailability
- Ischemic protection: Reduces toxic acyl-CoA accumulation
- Mild vasodilation: Modest BP reduction
Pharmacokinetics
| Parameter | Value | Significance |
|---|---|---|
| Oral bioavailability | ~78% | Good absorption |
| Tmax | 1–2 hours | Rapid onset |
| Plasma half-life | 3–6 hours | Short systemic half-life |
| Tissue retention | Weeks to months | Detectable in urine long after discontinuation; relevant to anti-doping |
| Elimination | Renal, mostly unchanged | Adjust in renal impairment |
Dosing & administration
Meldonium dosing varies by indication and individual factors. No FDA-approved dosing exists for this compound; protocols in the literature derive from limited clinical or preclinical data and practitioner experience.
Any use should be conducted under qualified medical supervision with appropriate monitoring of safety markers.
Important: These dosing ranges are not FDA-approved. Any use should be under qualified medical supervision.
Side effects & safety
Safety data for Meldonium is primarily derived from preclinical studies and limited human data. Long-term effects in humans remain incompletely characterized.
Common
- • Headache
- • Dyspepsia
- • Mild blood pressure changes
- • Tachycardia
- • Skin rash
Serious / potential risks
- • Arrhythmias (rare reports)
- • Hypersensitivity reactions
- • Theoretical concern about chronic carnitine deficiency
- • Banned for competitive athletes (WADA)
- • Limited long-term safety data in Western populations
Drug interactions
| Medication | Interaction | Recommendation |
|---|---|---|
| Antihypertensives and nitrates | Additive vasodilation and hypotension | Monitor blood pressure |
| L-carnitine supplementation | Antagonistic mechanism; reverses metabolic effect | Avoid combination if therapeutic intent is meldonium |
| Stimulants | Possible additive cardiovascular load | Caution in arrhythmia-prone patients |
Storage & handling
Lyophilized (powder)
- • Store at -20°C to 4°C (freezer or refrigerator)
- • Protect from light and moisture
- • Stable for 12–24 months when stored properly
- • Keep in original sealed container until reconstitution
Reconstituted solution
- • Refrigerate at 2–8°C after reconstitution
- • Use bacteriostatic water for multi-dose reconstitution
- • Typical stability: 14–28 days refrigerated
- • Do not freeze reconstituted solution
Cost & availability
| Source | Cost | Notes |
|---|---|---|
| Research suppliers | Varies widely | Quality and purity vary significantly between sources |
| Compounding pharmacies | Prescription required | Higher quality assurance and purity testing |
The bottom line
Meldonium is a metabolic compound with research interest in cardioprotection, metabolic shift, performance. While preclinical evidence is encouraging, it remains investigational and is not FDA-approved. Any use should be under qualified medical supervision.
Best for
- • Researchers studying metabolic regulation and energy homeostasis
- • Individuals interested in cardioprotection under medical guidance
Not for
- • Self-administration without medical supervision
- • Pregnant or breastfeeding individuals
- • Individuals with contraindicated conditions
Related compounds
Frequently asked questions
References
- [1] Dambrova M, Makrecka-Kuka M, Vilskersts R, et al.. Pharmacological effects of meldonium: Biochemical mechanisms and biomarkers of cardiometabolic activity. Pharmacol Res (2016). doi: 10.1016/j.phrs.2016.01.019 PMID: 26850121
- [2] Schobersberger W, Dünnwald T, Gmeiner G, Blank C.. Story behind meldonium—from pharmacology to performance enhancement: a narrative review. Br J Sports Med (2017). doi: 10.1136/bjsports-2016-097488 PMID: 28258177
- [3] Sjakste N, Gutcaits A, Kalvinsh I.. Mildronate: an antiischemic drug for neurological indications. CNS Drug Rev (2005). doi: 10.1111/j.1527-3458.2005.tb00043.x PMID: 16389295