Sarm - s4

[gymrat827]

S-40503 is an investigational selective androgen receptor modulator (SARM) developed by the Japanese company Kaken Pharmaceuticals, which was developed for the treatment of osteoporosis. SARMs are a new class of drugs which produce tissue-specific anabolic effects in some tissues such as muscle and bone, but without stimulating androgen receptors in other tissues such as in the prostate gland, thus avoiding side effects such as benign prostatic hypertrophy which can occur following treatment with unselective androgens like testosterone or anabolic steroids.[1]

S-4 is a SARM that shows good functional selectivity for bone tissue, and has relatively little effect on muscle mass and no observable effect on the prostate gland. In animal studies it was shown to increase both bone mineral density and biomechanical strength of femoral cortical bone, and at low doses showed anabolic effects only on bone tissue, while at higher doses both bone and muscle growth were affected, yet prostate gland enlargement was not seen at any dose tested.

The lack of virilizing effects means that S-40503 may even be suitable for use in women, which would be a substantial advantage over existing drugs as women tend to be more likely to suffer from osteoporosis, and are generally contraindicated from taking anabolic steroids due to the risk of side effects such as masculinisation and hirsutism.[2] Since these promising initial studies, no further data about S-40503 has been published by Kaken, and it is thought that rather than being developed for human use itself, S-40503 may be more likely to be used as a lead compound for the development of novel derivatives with similar bone anabolic effects, but longer in vivo half-life and better bioavailability.[3]

Selective androgen receptor modulators may also be used by athletes to assist in training and increase physical stamina and fitness, potentially producing effects similar to anabolic steroids but with significantly less side effects. For this reason, SARMs have already been banned by the World Anti-Doping Agency since January 2008 despite no drugs from this class yet being in clinical use, and blood tests for all known SARMs are currently being developed.[4][5]

References

^ Gao W, Dalton JT. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs). Drug Discovery Today. 2007 Mar;12(5-6):241-8. doi:10.1016/j.drudis.2007.01.003 PMID 17331889
^ Hanada K, Furuya K, Yamamoto N, Nejishima H, Ichikawa K, Nakamura T, Miyakawa M, Amano S, Sumita Y, Oguro N. Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis. Biological and Pharmaceutical Bulletin. 2003 Nov;26(11):1563-9. doi:10.1248/bpb.26.1563 PMID 14600402
^ Gao W, Kim J, Dalton JT. Pharmacokinetics and pharmacodynamics of nonsteroidal androgen receptor ligands. Pharmaceutical Research. 2006 Aug;23(8):1641-58. PMID 16841196
^ Thevis M, Kohler M, Schlörer N, Kamber M, Kühn A, Linscheid MW, Schänzer W. Mass spectrometry of hydantoin-derived selective androgen receptor modulators. Journal of Mass Spectrometry. 2008 May;43(5):639-50. doi:10.1002/jms.1364 PMID 18095383
^ Thevis M, Kohler M, Thomas A, Maurer J, Schlörer N, Kamber M, Schänzer W. Determination of benzimidazole- and bicyclic hydantoin-derived selective androgen receptor antagonists and agonists in human urine using LC-MS/MS. Analytical and Bioanalytical Chemistry. 2008 May;391(1):251-61. doi:10.1007/s00216-008-1882-6 PMID 18270691

 

[gymrat827]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2039878/




Results
We found that S-4 treatment maintained whole body and trabecular BMD, cortical content, and increased bone strength while decreasing body fat in these animals.

Conclusions
The data presented herein show the protective skeletal effects of S-4. Our previous reports have shown the tissue selectivity and muscle anabolic activity of S-4. Together these data suggest that S-4 could reduce the incidence of fracture via two different mechanisms (i.e., via direct effects in bone and reducing the incidence of falls through increased muscle strength). This approach to fracture reduction would be advantageous over current therapies in these patients which are primarily antiresorptive in nature.

also, very interesting when thinking about S4's affect on injuries:

DEXA, pQCT, and biomechanical strength testing on excised bones further validated the whole body DEXA results and support our hypothesis that SARMs inhibit bone loss. The L5–L6 BMD and the distal femur trabecular BMD data suggest that S-4 is a modest inhibitor of trabecular bone loss. We showed that the 0.5, 1.0, and 3.0 mg/day doses of S-4 were able to significantly increase BMD in the L5–L6 region and both 1.0 and 3.0 mg/day dose groups exhibited higher BMD in the distal femur.

DHT and S-4 significantly increased the maximum load required to break the femur compared to OVX controls. Further, S-4-treated groups showed a non-significant increase over DHT-treated controls. The effects of S-4 treatment on cortical bone were similar to those reported by Hanada et al. (26) during their evaluation of the anabolic effects of S-40503, in a rat model of osteoporosis. They concluded that S-40503 was anabolic in cortical bone (30 mg/kg dose).

S-4 is more potent than S-40503 in bone and levator ani muscle and more tissue selective (i.e., S-4 fully restored levator ani muscle weight at a dose that only restored the prostate to 34% of intact

 

[gymrat827]

"The primary circulating and the most significant biologically active androgen in women is testosterone (21). However, aromatization to estradiol makes it difficult to delineate the androgenic versus estrogenic action of testosterone. Therefore, we included DHT, which cannot be aromatized, as a positive control group for the AR-mediated actions in this model. While DHT partially prevented some of the OVX-induced changes, DHT treatment in intact animals caused some detrimental effects. These effects were most likely due to the ability of DHT to inhibit luteinizing hormone (LH) and follicle stimulating hormone (FSH) release from the pituitary. Therefore, DHT indirectly inhibited production of ovarian hormones, in effect, pharmacologically ovariectomizing the intact animals. Further studies are needed to validate this hypothesis as estrogen levels were not measured in this study. Other studies in our laboratory have shown that S-4 does not affect LH or FSH levels (data not shown), highlighting an important difference between steroidal AR agonists and nonsteroidal SARMs."

 

[gymrat827]

They were saying the same thing 6 years ago, i still dont see a SARM out there that does anything...

which ones have you tried?? i got great results from osta + S4. the gains are not like AAS but much better than OTC supps.

 

[gymrat827]

It is a sarm, a selective androgen receptor modulator, of the sarms currently being studied (s4 studies have been stopped due to the toxic effects of the metabolite M1 that binds to the occular receptor, the heart and other organs) s4 is the weakest in anabolic activity, but one of the most androgenic, being 1/3 as strong as testosterone at binding to the androgen receptor.
Dont look at the info on wikipedia half the stuff is wrong, this does not reduce the size of the prostate. It will over time enlarge it, and it does cause suppression, though its mild.
The best part of s4 is the fact that it causes a drying out of the muscle and the skin surrounding it, and in turn it binds very well to the androgen muscle receptors, Hardening and sharpening the muscle, so towards the end of a cycle it would proove to be very effective.
SARMS s4 causes significant weight loss by binding to the androgen receptors it allows for fat to be oxidised, and this also makes it very usefull.

 

[PillarofBalance]

I'm still waiting for the yellow vision to kick in at 75mg per day... Thinking of bumping to 100

 

[gymrat827]

i never got it..... but only went to 85-90mg tops. I had issues coming from outdoor bright light to indoor dim light. it was very odd too. you ll know when it happens.