Selective androgen receptor modulators (SARMs)

Selective androgen receptor modulators (SARMs) #

Selective androgen receptor modulators, or SARMs, work on the same principle as SERMs – selective estrogen receptor modulators, which include the well-known clomiphene and tamoxifen. SARMs are able to bind to and interact with receptors for male sex hormones – androgens. SARMs have a different structure to anabolic steroids and are not affected by enzymes that convert testosterone into other compounds with undesirable health effects.

The aim of the development of this class of drugs was to reduce the adverse effects of testosterone on the prostate. As is standard practice, substances and compounds are first tested on animals; if they show positive effects and safety is confirmed, they are then tested in humans in clinical trials before going into production. Often, positive results in rats are all that is needed for the drug to come to the attention of “chemical” athletes, who then begin to test it themselves.

Much the same happened with SARMs – as soon as James Dalton’s creation was mentioned in the open literature, and it was claimed that taking them would lead to an increase in muscle mass, they immediately found themselves illegally in the hands of bodybuilders. One of the first, despite the ambiguous conclusions of the research, including Andarine, better known in the world of sport as “S4”. This was followed almost immediately by Ostarine, known as GTX-024. Both SARMs were widely available in online shops before there was any official proof that Ostarine really did promote muscle growth in humans and was relatively safe to use. However, in high performance sports where anti-doping controls are a threat, Ostarine is an extremely risky and undesirable drug, as its metabolites are detected within three months or more, depending on the dose and the individual athlete’s metabolic characteristics.

In September 2011, the Journal of Cachexia, Sarcopenia and Muscle published an article entitled “The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial”. This article presents the results of GTx-024 use, which the scientists considered to be statistically significant: a 12-week course of oral administration of 3 mg of the drug resulted in an increase in dry muscle mass of 1.4 kg and a reduction in fat mass of 300 grams in the absence of any physical activity. Lower doses of the drug produced less pronounced results. The official conclusion of the researchers was as follows GTx-024 showed a dose-dependent improvement in total muscle mass and physical function and was well tolerated. GTx-024 may be useful in the prevention and/or treatment of muscle wasting associated with cancer and other chronic diseases. Perhaps 1.4kg of muscle mass in 12 weeks is not that much, but it is an officially achieved and recorded result.

At present, pharmaceutical companies have several types of SARMs that have successfully completed the first stages of clinical trials in humans and may soon appear on the legal market, and by that time the practice of their use for sporting purposes will certainly have formed, but for now, even from a small amount of the above information, you can get an idea of the dosage, duration of administration and side effects.

Research data #

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At present, no selective androgen receptor modulator is truly selective. They just have a higher anabolic index, with a ratio of anabolic to androgenic activity ranging from 3:1 to 10:1 (testosterone has a ratio of 1:1) [1] [2] [3].

Almost all selective androgen receptor modulators are available in tablet form and do not cause liver damage [4].

This is the best choice for women as they have minimal effects on libido, sexual characteristics, blood cholesterol, liver, etc. [5].

SARM’S legal status #

Most of SARM’S are legal. In judicial practice, SARM’s are highly likely to be recognized as medicines.

Since the early twenty-first century, SARMs have been used in doping; they were banned by the World Anti-Doping Agency in 2008. SARMs are readily available on internet and are commonly used recreationally to stimulate muscle growth.

SARMs test stages #

Clinical trials:

• Ostarine (GTx-024, MK-2866, S-22) – acts on bone and muscle tissue [6]
• BMS-564,929 – acts mainly on muscle tissue
• Ligandrol (LGD-4033, VK5211, Anablicum) – acts on bone and muscle tissue
• Testolone (RAD140, EP0062, Radarine, Radium, Vosilasarm) – in addition to the anabolic effect, it increases endurance and has a neuroprotective effect [16] [17] [18] [19]

Preclinical trials:

• AC-262,356 (Accadine, Sarmastol) [7]
• JNJ-28330835 [8] [9]
• LGD-2226 – affects bone and muscle
• LGD-3303 [10]
• S-23 (Mastorin) – as a male contraceptive [12] [13]
• Myostine (YK-11, Myostan, Myostan, Miostop) – Japanese SARM in development, is also a myostatin inhibitor [14] [15]
• ACP-105

Discontinued:

• Andarine (S-4, GTx-007, S-40503) – acts mainly on bone tissue (treatment of osteoarthritis) [11]
• ⚠️ Cardarine (Cardarine, Endurobol, Peroximod, Hennos, GW-501516) – studies discontinued due to carcinogenic effects

Other (not classified as SARMs):

• Reverol (SR9009, Reverol, Edrophonium, Endorol, Stenabol) – an oral compound developed by the Scripps Research Institute. The main effects are increased endurance (due to the formation of new mitochondria), treatment of obesity, muscle hypertrophy. The mechanism of action is to bind to the Rev-ErbA alpha molecule in the body, which has various regulatory functions [21]
• Recardin (SR9011) – analogue of SR9009 [22]
• Ibutamoren – (Ibutamoren, Nutrobal, MK-677) is an oral growth hormone secretion stimulator.
• Laxogenin (5a-hydroxy-laxogenin or Anogenin)is a plant steroid that was studied by the Japanese in the 1960s [23] and is currently being actively promoted in sport, although no beneficial effects have been proven in humans.
• AICAR – increases endurance [24]

See also #

• Peptides
• Melanotan 2
• Ostarine
• Ligandrol
• Testolone
• Ibutamoren
• Andarine
• S-23
• Recardin
• ACP-105
• Myostine
• LGD-3303

References #

1. Yin D, Gao W, Kearbey JD, Xu H, Chung K, He Y, Marhefka CA, Veverka KA, Miller DD, Dalton JT (March 2003). “Pharmacodynamics of Selective Androgen Receptor Modulators”. J. Pharmacol. Exp. Ther. 304 (3): 1334–40.  PMID: 12604714 DOI: 10.1124/jpet.102.040840
2. Hanada K, Furuya K, Yamamoto N, Nejishima H, Ichikawa K, Nakamura T, Miyakawa M, Amano S, Sumita Y, Oguro N (November 2003). “Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis”. Biol. Pharm. Bull. 26 (11): 1563–9.
   PMID: 14600402 DOI: 10.1248/bpb.26.1563
3. Ostrowski J, Kuhns JE, Lupisella JA, Manfredi MC, Beehler BC, Krystek SR, Bi Y, Sun C, Seethala R, Golla R, Sleph PG, Fura A, An Y, Kish KF, Sack JS, Mookhtiar KA, Grover GJ, Hamann LG (January 2007). “Pharmacological and x-ray structural characterization of a novel selective androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats”. Endocrinology 148 (1): 4–12.
4. Zhang X, Li X, Allan GF, Sbriscia T, Linton O, Lundeen SG, Sui Z (August 2007). “Design, synthesis, and in vivo SAR of a novel series of pyrazolines as potent selective androgen receptor modulators”. J. Med. Chem. 50 (16): 3857–69.
5. Negro-Vilar A (1999). “Selective androgen receptor modulators (SARMs): a novel approach to androgen therapy for the new millennium”. J. Clin. Endocrinol. Metab. 84 (10): 3459–62.
6. M.S. Steiner et al. (June 2010). “Effect of GTx-024, a selective androgen receptor modulator (SARM), on stair climb performance and quality of life (QOL) in patients with cancer cachexia”. J Clin Oncol 28 (1534).
7. Piu F, Gardell LR, Son T, Schlienger N, Lund BW, Schiffer HH, Vanover KE, Davis RE, Olsson R, Bradley SR. Pharmacological characterization of AC-262536, a novel selective androgen receptor modulator J. Steroid Biochem. Mol. Biol. 129–37 2008
8. Zhang X, Li X, Allan GF, Sbriscia T, Linton O, Lundeen SG, Sui Z (January 2007). “Serendipitous discovery of novel imidazolopyrazole scaffold as selective androgen receptor modulators”. Bioorganic & Medicinal Chemistry Letters 17 (2): 439–43.
9. Allan GF, Tannenbaum P, Sbriscia T et al. (2007). “A selective androgen receptor modulator with minimal prostate hypertrophic activity enhances lean body mass in male rats and stimulates sexual behavior in female rats”. Endocrine 32 (1): 41–51.
10. Vajda EG, López FJ, Rix P, Hill R, Chen Y, Lee KJ, O’Brien Z, Chang WY, Meglasson MD, Lee YH (February 2009). “Pharmacokinetics and pharmacodynamics of LGD-3303 [9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo-[3,2-f]quinolin-7(6H)-one], an orally available nonsteroidal-selective androgen receptor modulator”. J. Pharmacol. Exp. Ther. 328 (2): 663–70.
11. http://lifebio.wiki/s-40503
12. http://lifebio.wiki/s-23
13. Jones A, Chen J, Hwang DJ, Miller DD, Dalton JT (January 2009). “Preclinical Characterization of a (S)-N-(4-Cyano-3-Trifluoromethyl-Phenyl)-3-(3-Fluoro, 4-Chlorophenoxy)-2-Hydroxy-2-Methyl-Propanamide: A Selective Androgen Receptor Modulator for Hormonal Male Contraception”. Endocrinology 150 (1): 385–95.
14. http://lifebio.wiki/yk11
15. Kanno Y, Ota R, Someya K, Kusakabe T, Kato K, Inouye Y (2013). “Selective androgen receptor modulator, YK11, regulates myogenic differentiation of C2C12 myoblasts by follistatin expression”. Biol. Pharm. Bull. 36 (9): 1460–5. doi:10.1248/bpb.b13-00231. PMID 23995658.
16. http://lifebio.wiki/rad140
17. Jayaraman A, Christensen A, Moser VA, Vest RS, Miller CP, Hattersley G, Pike CJ (Apr 2014). “Selective androgen receptor modulator RAD140 is neuroprotective in cultured neurons and kainate-lesioned male rats”. Endocrinology 155 (4): 1398–406. doi:10.1210/en.2013-1725. PMC 3959610. PMID 24428527.
18. Hamson DK, Wainwright SR, Taylor JR, Jones BA, Watson NV, Galea LA (Sep 2013). “Androgens increase survival of adult-born neurons in the dentate gyrus by an androgen receptor-dependent mechanism in male rats”. Endocrinology 154 (9): 3294–304. doi:10.1210/en.2013-1129. PMID 23782943.
19. Miller CP, Shomali M, Lyttle CR, O’Dea LS, Herendeen H, Gallacher K, Paquin D, Compton DR, Sahoo B, Kerrigan SA, Burge MS, Nickels M, Green JL, Katzenellenbogen JA, Tchesnokov A, Hattersley G (Feb 2011). “Design, Synthesis, and Preclinical Characterization of the Selective Androgen Receptor Modulator (SARM) RAD140”. ACS Medicinal Chemistry Letters 2 (2): 124–9. doi:10.1021/ml1002508. PMC 4018048. PMID 24900290.
20. http://lifebio.wiki/s-4-андарин
21. http://lifebio.wiki/sr9009
22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085709/
23. http://www.ncbi.nlm.nih.gov/pubmed/14041495
24. http://lifebio.wiki/aicar