An experimental drug that mimics the effect of steroids, such as testosterone, without many of the harmful side effects is freely available online, according to new research. A group from the German Sport University Cologne in Germany detected the compound in a product called Andarine, available online for $100 and labeled as green tea extracts and face moisturizer. The research appears in the current issue of the journal Drug Testing and Analysis.

Known as selective androgen receptor modulators, or SARMs, the drugs are being developed for diseases such as muscle-wasting and osteoporosis. The World Anti-Doping Agency, an international, independent organization based in Lausanne, Switzerland, that coordinates anti-doping regulations across sports, banned the drugs last year, before any of them were approved for medical use, in recognition of the molecules' potential allure to sports dopers, and athletes' willingness to take even experimental compounds. Since then, the agency has quietly been working with scientists across the globe to develop new tests to detect illegal use of the compounds.

According to a previous TR article on sports doping,

These drugs represent "a whole new horizon for anabolic therapies, and the potential for abuse will be exceedingly high," says William Evans, director of the Nutrition, Metabolism, and Exercise Laboratory at the University of Arkansas for Medical Sciences.

SARMs work similarly to testosterone but in a more targeted way. "They are effective by binding to the steroid receptor in only specific tissue, like muscle," says Evans, who is also a scientific advisor to GTx, a company developing the drugs. "They are not steroid drugs, but they produce the anabolic effect of the steroids." GTx, based in Memphis, TN, has shown in a clinical trial that one compound being developed for muscle wasting and bone loss can significantly boost lean muscle mass in older people.

According to a press release from the journal,

Mario Thevis, Ph.D., and colleagues, analyzed the advertised substance using state-of-the-art mass spectrometric approaches with high resolution/high accuracy (tandem) mass spectrometry. "One unit (30 mL) was purchased online and delivered in a box labeled to contain face moisturizer and green tea extract. The sealed bottle did not declare any content and no further documents accompanied package," said Dr. Thevis. He went on to explain that LC-MS(/MS) analysis of this solution revealed the presence of S-4 at approximately 150 mg/mL with equal amounts in each container, yielding a total of 4.5 g of the SARM. The active ingredient was identified and characterized by a) its elemental composition (as determined by high resolution/high accuracy mass spectrometry, b) comparison to synthesized reference material regarding retention time and product ion mass spectrum, and c) elucidation of its mass spectrometric behavior. Besides the detection of the active ingredient S-4, a significant amount of byproduct was observed.

"Major concerns result from these findings," explained Dr. Thevis. "This product with considerable anabolic properties is readily available without sufficient research on its undesirable effects; this is especially significant where uncontrolled dosing is applied and drug impurities with unknown effects are present in considerable amounts as observed in the studied material."

The issue was recently addressed at the Conference of Parties to the International Convention against Doping in Sport, held October 26-28, 2009 at the United Nations Educational, Scientific and Cultural Organization's (UNESCO) headquarters in Paris. WADA President John Fahey said that government agencies will need to adopt laws and regulations to combat the trafficking and supply of illegal substances in order to rid sport of doping.

The ease of purchasing SARMs as a performance-enhancing drug supports the need to make early implementation of screening for emerging therapeutic compounds a routine part of sports drug testing. "Our study demonstrates once more that the misuse of therapeutics without clinical approval by athletes cannot be dismissed," Dr. Thevis concludes.

The red-blood-cell-boosting hormone erythropoietin (EPO), which is used clinically to treat anemia and illegally by athletes to boost endurance, may also improve brainpower. According to research published in the journal BMC Biology, mice treated with the drug performed better in certain learning and memory tests than did control animals.

EPO is popular among dopers because it increases blood oxygenation, mimicking the effect of blood doping. But it also targets the nervous system, improving survival of brain cells. The drug is currently in clinical trials for traumatic brain injury and stroke. (A previous post describes how EPO blocks brain swelling after trauma.)

The new research looks at how the drug affects a healthy brain. According to a press release issued by the journal,

[Hannelore] Ehrenreich [from the Max Planck Institute of Experimental Medicine, in Göttingen, Germany] and her colleagues tested the effects of erythropoietin on the ability of the mice to learn how to exploit an experimental set-up to receive sugared water. Over a series of learning stages, the mice were trained to get their treat by poking their noses into holes lit by LEDs, rather than into unlit holes, within a time limit. The mice that had been treated with recombinant human erythropoietin were significantly more likely to master the task than those that had not. According to Ehrenreich, "Treated mice showed superior performance in associative, operant and discriminant learning as well as in the initial training phases. Moreover, erythropoietin-treated mice demonstrated better task adaptation and higher performance stability."

The researchers conclude, "Further untangling of molecular mechanisms of erythropoietin action on higher cognitive functions may ultimately open new avenues for prevention strategies and therapeutic interventions in neuropsychiatric diseases."

Some athletes and trainers are tuned in to the drug-development pipeline, looking for the next big doping agent: experimental drugs that can boost strength and endurance but are new enough to slip under the screening radar. One scientist I spoke to for a previous piece on doping said that he still gets flooded with calls from athletes years after publishing details of a promising advance in drug development for muscular dystrophy.

In an effort to combat the abuse of new compounds before it starts, anti-doping agencies have begun working with drug companies to develop screening tests before drugs are even on the market. In last year's Tour de France, the World Anti-Doping Agency caught several cyclists using a longer-lasting form of the endurance booster EPO (erythropoietin), called CERA. Soon after the athletes were caught, it was revealed that the agency had been working with Swiss drugmaker Roche to develop a test to detect CERA while the drug was still being tested by the U.S. pharmaceutical company Amgen.

Now German scientists announce that they have developed a test for a class of compounds called benzothiazepines, which are being developed for the treatment of heart abnormalities and have been shown to boost endurance in mice. According to a press release from Drug Testing and Analysis, the journal publishing the research,

These compounds stabilize protein channels that would otherwise "leak" calcium from muscle cells during strenuous exercise. Calcium is needed for muscle contraction and this "leaking" effect weakens the contractions and is a causal factor in muscle fatigue.

While the drugs have not yet been tested in humans, researchers say that they carry a high potential for abuse because they are easy to make.

"As soon as these drugs enter human clinical trials, there is a huge potential for them to be misused in sports. This preventive research lets us prepare before these compounds are officially launched," says Mario Thevis, Director of the Center for Preventive Doping Research at the German Sport University of Cologne, Germany, who led the research.

The study characterises the compounds according to their weight and molecular structure. This gives the researchers a molecular "fingerprint" by which to identify the compounds. Thevis and colleagues show that, using high resolution mass spectrometry, JTV-519 and S-107 can be detected in spiked urine at concentrations as low as 0.1 nanograms per millilitre.