I will freely admit that I had never heard of meldonium (aka mildronate) until yesterday, when it made headlines across the sports pages (and cost Maria Sharapova a great deal of endorsement money). That’s probably because it’s never been approved in the US or anywhere in Western Europe. That category of drugs is a relatively small and very mixed bag. Very few countries have companies or institutes that actually develop new drugs, and once you get past North America, Western Europe, and Japan things thin out pretty rapidly. India and China have only started getting into from-the-ground-up drug discovery business relatively recently, so you have Israel, Australia, and not too many others once you get outside the three regions mentioned above.
But eastern Europe and the former Soviet Union are a case all by themselves. The division of Europe during the cold war era caused two parallel scientific worlds to develop, and there were two worlds in the pharmaceutical business as well. There were (and are) extremely capable chemists and biologists in Russia, Ukraine, the Baltic states, former Czechoslovakia, Hungary, East Germany, Poland, etc., and a lot of pharmaceutical R&D was done during the cold war years that never really mixed with the West. Those readers who remember the Warsaw Pact chemistry and biology journals know about the sheer volume of work that came out of these countries (although from what I’m told, there was often a justify-your-relatively-good-job-comrade aspect to all this publishing).
Meldonium is one of these. It came out of Latvia in the 1970s, and the only places where it’s an approved drug appear to be parts of the former Soviet Union. There can be several reasons for this sort of cold-war hangover in approval, but I have no problem invoking my standard answer to questions that start off with “I wonder how come they. . .”, which is “Money”. Drugs that were approved under the old government(s) in this region have by and large been carried over until today, and seeking approval in the EU or the US is an expensive proposition for something whose patentability is shot.
But there are other factors. An outstanding drug caught in that situation could easily be the subject of some research to produce a newer derivative or improved formulation that would be patentable, but when you haven’t seen that happen, it increases the chances that the drug itself is something that probably wouldn’t find much of a niche. Meldonium, though, has been the subject of recent clinical work in several countries, generally in people who’ve had heart attacks or strokes. It’s prescribed for ischemia in cardiac patients, and the increased blood flow is surely the reason that it’s caught on among some athletes. Sharapova’s claim that she has been taking it for years for “medical reasons” doesn’t sound very plausible, at least at first, considering what the approved patient population looks like – they tend not to have very effective backhand strokes.
She claims to suffer from magnesium deficiency and a family history of diabetes, but I’m having trouble drawing a line from those to meldonium. Most of the time when people talk about a family history of diabetes they mean something like Type I or MODY, either of which would have presumably shown up long since in Sharparova’s case. And a professional athlete would seem to be at little risk of Type II, with its strong connection to weight gain and lack of exercise. As for magnesium deficiency, that’s a staple of “Could You Have This Common Disease?” columns, usually with reference to vague symptoms (tiredness!) that everyone feels. Magnesium is not a particularly rare element in a varied human diet and it can be easily supplemented. A true problem with its absorption is something that can be demonstrated clinically. Unless Sharapova has something to back that diagnosis up, it’s not very solid, either.
The compound – a very simple structure – appears to work as an inhibitor in the carnitine biosynthesis pathway, and may have several other activities. Landing in that pathway might well be enough all by itself; metabolically, there’s a lot going on at that intersection. The World Anti-Doping Agency has now banned it, on the basis of studies that say that it increases endurance, speeds recovery, protects against stress, and may have CNS effects as well. Unless more evidence comes to light, I’d say that this case is exactly what it looks like.