Selective androgen receptor modulator

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Selective androgen receptor modulators , or SARMS for short , are a new class of androgen receptor binding substances. In their effects they are similar to anabolic and androgenic steroids .

The currently best known and researched are Ostarine and Andarine (S-4). Both drugs are currently not approved as drugs, but are mostly marketed by Chinese manufacturers in Europe and the USA, although the active ingredient content of these products is controversial. Ostarine is managed and researched by the pharmaceutical company GtX as "enobosarm" (Ostarine®; GTx-024). It is considered a potential drug to treat muscle wasting and other muscle diseases.

The binding affinity to the androgen receptor is stronger than that of testosterone , studies indicate up to ten times this. Research into nonsteroidal androgens has continued since 1998. In these studies, it was found that SARMS work primarily in anabolic tissues such as muscles, while they affect androgenic tissues (e.g. prostate ) far less. Some SARMs also have a beneficial effect on bone tissue, similar to nandrolone .

There are currently no studies on humans, studies on animals exist. One of the most promising SARMs is called S-1, short for 3- (4-fluorophenoxy) -2-hydroxy-2-methyl-N- [4-nitro-3-5 (trifluoromethyl) phenyl] propanamide. In castrated rats, i.e. rats that do not produce their own testosterone, S-1 is able to maintain the bulk of the muscles for the most part, while typical androgenic tissues, such as the prostate, respond many times less. Even in healthy (non-castrated) test animals, S-1 inhibits the testosterone effect in androgenic tissues by binding to the androgen receptors there, but only having a minor effect - the occupied receptors are therefore inaccessible to testosterone. SARMs are thus considered to be partial AR agonists in androgenic tissues and full AR agonists in anabolic tissues, which means that the criterion of selectivity is met.

Newer SARMs such as S-1, S-2, S-3 have an androgenic effect of 3-15% compared to dihydrotestosterone , with an anabolic activity of almost 100 percent. The different SARMs have different effects on the pituitary gland . Some act agonistically on the androgen receptors of the pituitary gland and consequently inhibit the production of LH and FSH and thus testosterone production, while other SARMs do not have this special effect.

The World Anti-Doping Agency (WADA) put the group of SARMs on the prohibited list since January 1st, 1998. The Doping Substance Quantity Ordinance put them on the list on January 1, 2013 and specified the amount of possession that is punishable under the Medicines Act as a “not insignificant amount” according to the Medicines Act . SARMs have been proven in doping drug tests since 2008 at the latest. To do this, the target substances are extracted from the urine and identified with the help of chromatographic and mass spectrometric systems.

Individual evidence

  1. ↑ ML Mohler, CE Bohl, A. Jones, CC Coss, R. Narayanan, Y. He, DJ Hwang, JT Dalton, DD Miller: Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit . In: Journal of Medicinal Chemistry . tape 52 , no. June 12 , 2009, p. 3597-3617 , doi : 10.1021 / jm900280m , PMID 19432422 .
  2. ↑ M. Thevis, M. Kohler, J. Maurer, N. Schlörer, M. Kamber, W. Schänzer: Screening for 2-quinolinone-derived selective androgen receptor agonists in doping control analysis. In: Rapid Commun. Mass Spectrom. 21, 2007, pp. 3477-3348.
  3. ↑ JT Dalton, A. Mukherjee, Z. Zhu, L. Kirkovsky, DD Miller: Discovery of nonsteroidal androgens. In: Biochem Biophys Res Commun. 244 (1), 1998, pp. 1-4.
  4. ↑ M. Thevis, M. Kamber, W. Schanzer: Screening for metabolically stable aryl-propionamide-derived selective androgen receptor modulators for doping control purposes. In: Rapid Commun Mass Spectrom. 20 (5), 2006, pp. 870-876.
  5. ↑ JD Kearbey, D. Wu, W. Gao, DD Miller, JT Dalton: Pharmacokinetics of s-3 in rats, a non-steroidal selective androgen receptor modulator. In: Xenobiotica. 34, 2004, pp. 273-280.
  6. ^ Mario Thevis, Wilhelm Schänzer : Doping substances of the future and their evidence. In: The science magazine. 1, 2009, pp. 14-17. (Doping info: SARMS)