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  1. #61
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    yet another SARM
    1: J Pharmacol Exp Ther. 2009 Feb;328(2):663-70. Epub 2008 Nov 18. Links
    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.Vajda EG, L?pez FJ, Rix P, Hill R, Chen Y, Lee KJ, O'Brien Z, Chang WY, Meglasson MD, Lee YH.

    Selective androgen receptor modulators (SARMs) are a new class of molecules in development to treat a variety of diseases. SARMs maintain the beneficial effects of androgens, including increased muscle mass and bone density, while having reduced activity on unwanted side effects. The mechanisms responsible for the tissue-selective activity of SARMs are not fully understood, and the pharmacokinetic (PK)/pharmacodynamic (PD) relationships are poorly described. Tissue-specific compound distribution potentially could be a mechanism responsible for apparent tissue selectivity. We examined the PK/PD relationship of a novel SARM, LGD-3303 [9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo[3,2-f]quinolin-7(6H)-one], in a castrated rat model of androgen deficiency. LGD-3303 has potent activity on levator ani muscle but is a partial agonist on the preputial gland and ventral prostate. LGD-3303 never stimulated ventral prostate above intact levels despite increasing plasma concentrations of compound. Tissue-selective activity was maintained when LGD-3303 was dosed orally or by continuous infusion, two routes of administration with markedly different time versus exposure profiles. Despite the greater muscle activity relative to prostate activity, local tissue concentrations of LGD-3303 were higher in the prostate than in the levator ani muscle. LGD-3303 has SARM properties that are independent of its pharmacokinetic profile, suggesting that the principle mechanism for tissue-selective activity is the result of altered molecular interactions at the level of the androgen receptor.
    PMID: 19017848 [PubMed - in process]
    Disclaimer: While I have an M.D. the views I express are not to be taken as medical advice under any circumstances. Please check with your own doctor if you want medical advice as he/she has access to your info and can provide the most accurate advice.


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  2. #62
    Banned Patrick Arnold's Avatar
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    Originally Posted by Dr.Dave1 View Post
    yet another SARM

    SARMs are no different than anabolic steroids in the pharmacological sense.

    what is exciting about them however is the possibility that they may provide even greater differentiation between anabolic and androgenic effects than synthetic steroidal androgens have been able to acheive. IN reality though, this aspect is really only exciting for females

  3. #63
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    Originally Posted by Patrick Arnold View Post
    IN reality though, this aspect is really only exciting for females
    How so? Aren't androgenic sides the main cause for the nasty sides in men as well? In fact aren't most of the nasty sides people try to avoid with AAS-androgen related?

    I'm a noob in this field, but that was my impression, or am I completely off-base here?

    p.s.

    I remember you talking righ after the PH ban that there will NEVER EVER be anything that achieves anabolic effects without being hormonal. Kinda like bill-gates claimed no one will ever have more than 640k of memory heheh.

  4. #64
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    new review of SARMS . . . looks like a good topic review although I have not seen the full text
    1: Curr Opin Clin Nutr Metab Care. 2009 May;12(3):232-40.Links
    Selective androgen receptor modulators as function promoting therapies.
    Bhasin S, Jasuja R.

    PURPOSE OF REVIEW: The past decade has witnessed an unprecedented discovery effort to develop selective androgen receptor modulators (SARMs) that improve physical function and bone health without adversely affecting the prostate and cardiovascular outcomes. This review describes the historical evolution, the rationale for SARM development, and the mechanisms of testosterone action and SARM selectivity. RECENT FINDINGS: Although steroidal SARMs have been around since the 1940s, a number of nonsteroidal SARMs that do not serve as substrates for CYP19 aromatase or 5alpha-reductase, act as full agonists in muscle and bone and as partial agonists in prostate are in development. The differing interactions of steroidal and nonsteroidal compounds with androgen receptor (AR) contribute to their unique pharmacologic actions. Ligand binding induces specific conformational changes in the ligand-binding domain, which could modulate surface topology and protein-protein interactions between AR and coregulators, resulting in tissue-specific gene regulation. Preclinical studies have demonstrated the ability of SARMs to increase muscle and bone mass in preclinical rodent models with varying degree of prostate sparing. Phase I trials of SARMs in humans have reported modest increments in fat-free mass. SUMMARY: SARMs hold promise as a new class of function promoting anabolic therapies for a number of clinical indications, including functional limitations associated with aging and chronic disease, frailty, cancer cachexia, and osteoporosis.

    new SARM, orally bioavailable, high potency (for SARMS)
    1: J Med Chem. 2009 Apr 7. [Epub ahead of print]Click here to read Links
    N-Aryl-oxazolidin-2-imine Muscle Selective Androgen Receptor Modulators Enhance Potency through Pharmacophore Reorientation (dagger) ( big up tri, open).
    Nirschl AA, Zou Y, Krystek SR, Sutton JC, Simpkins LM, Lupisella JA, Kuhns JE, Seethala R, Golla R, Sleph PG, Beehler BC, Grover GJ, Egan D, Fura A, Vyas VP, Li YX, Sack JS, Kish KF, An Y, Bryson JA, Gougoutas JZ, Dimarco J, Zahler R, Ostrowski J, Hamann LG.


    A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model.
    Disclaimer: While I have an M.D. the views I express are not to be taken as medical advice under any circumstances. Please check with your own doctor if you want medical advice as he/she has access to your info and can provide the most accurate advice.


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  5. #65
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    looks like SARMS may even have uses for elderly females . . . good in that it may convince pharmaceutical companies to continue research

    1: Pharm Res. 2009 Sep 1.
    Effects of Selective Androgen Receptor Modulator (SARM) Treatment in Osteopenic Female Rats.
    Kearbey JD, Gao W, Fisher SJ, Wu D, Miller DD, Dalton JT.

    PURPOSE: Although androgens are known to protect bone, side effects and poor oral bioavailability have limited their use. We previously reported that S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (S-4) is a potent and tissue-selective androgen receptor modulator (SARM). This study was designed to evaluate the skeletal effects of S-4 in an osteopenic model. METHODS: Aged female rats were gonadectomized or sham operated on day 1 and assigned to treatment groups. Dosing was initiated on day 90 and continued daily until day 210. Whole animal bone mineral density (BMD), body weight, and fat mass were determined by dual energy x-ray absorptiometry (DEXA). Regional analysis of excised bones was performed using DEXA or computed tomography. Femur strength was evaluated by 3-point bending. RESULTS: S-4 restored whole body and lumbar vertebrae (L5-L6) BMD to the level of intact controls. Significant increases in cortical bone quality were observed at the femoral midshaft, resulting in increased load bearing capacity. CONCLUSIONS: S-4 demonstrated partial/complete recovery of bone parameters to age-matched intact levels. Increased efficacy observed in cortical bone sites is consistent with reported androgen action in bone. The ability of S-4 to promote bone anabolism, prevent bone resorption, and increase skeletal muscle mass/strength positions these drugs as promising new alternatives for the treatment of osteoporosis.
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  6. #66
    Registered User Harpagan's Avatar
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    Some news about S4: http://www.ergo-log.com/s4.html

  7. #67
    BOZZ is a phaggot ZachSmash's Avatar
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    Originally Posted by Harpagan View Post
    i read that a while ago. the price should come down in a couple years. maybe even in one year. too expensive right now, but i definitely wanna give it a whirl!
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  8. #68
    Busy Dude Dr.Dave1's Avatar
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    SARM S-23 can attenuate glucocorticoid muscle wasting . . . probably not applicable to most here but interesting none the less

    Endocrinology. 2010 Aug;151(8):3706-19. Epub 2010 Jun 9.
    Effects of a novel selective androgen receptor modulator on dexamethasone-induced and hypogonadism-induced muscle atrophy.

    Jones A, Hwang DJ, Narayanan R, Miller DD, Dalton JT.

    Glucocorticoids are the most widely used antiinflammatory drugs in the world. However, prolonged use of glucocorticoids results in undesirable side effects such as muscle wasting, osteoporosis, and diabetes. Skeletal muscle wasting, which currently has no approved therapy, is a debilitating condition resulting from either reduced muscle protein synthesis or increased degradation. The imbalance in protein synthesis could occur from increased expression and function of muscle-specific ubiquitin ligases, muscle atrophy F-box (MAFbx)/atrogin-1 and muscle ring finger 1 (MuRF1), or decreased function of the IGF-I and phosphatidylinositol-3 kinase/Akt kinase pathways. We examined the effects of a nonsteroidal tissue selective androgen receptor modulator (SARM) and testosterone on glucocorticoid-induced muscle atrophy and castration-induced muscle atrophy. The SARM and testosterone propionate blocked the dexamethasone-induced dephosphorylation of Akt and other proteins involved in protein synthesis, including Forkhead box O (FoxO). Dexamethasone caused a significant up-regulation in the expression of ubiquitin ligases, but testosterone propionate and SARM administration blocked this effect by phosphorylating FoxO. Castration induced rapid myopathy of the levator ani muscle, accompanied by up-regulation of MAFbx and MuRF1 and down-regulation of IGF-I, all of which was attenuated by a SARM. The results suggest that levator ani atrophy caused by hypogonadism may be the result of loss of IGF-I stimulation, whereas that caused by glucocorticoid treatment relies almost solely on up-regulation of MAFbx and MuRF1. Our studies provide the first evidence that glucocorticoid- and hypogonadism-induced muscle atrophy are mediated by distinct but overlapping mechanisms and that SARMs may provide a more effective and selective pharmacological approach to prevent glucocorticoid-induced muscle loss than steroidal androgen therapy.
    Disclaimer: While I have an M.D. the views I express are not to be taken as medical advice under any circumstances. Please check with your own doctor if you want medical advice as he/she has access to your info and can provide the most accurate advice.


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  9. #69
    Banned De__eB's Avatar
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    Originally Posted by Dr.Dave1 View Post
    SARM S-23 can attenuate glucocorticoid muscle wasting . . . probably not applicable to most here but interesting none the less

    which pharma is doing S-23?

  10. #70
    Registered User smt1's Avatar
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    Originally Posted by De__eB View Post
    which pharma is doing S-23?
    GTx (they brought toremifene to market, I believe)

    http://en.wikipedia.org/wiki/S-23_%28drug%29

  11. #71
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    Not recommending it but it's interesting to me that there are studies considering the possible use of Tren and 19-Nor in the realm of SARMS

    Am J Physiol Endocrinol Metab. 2011 Apr;300(4):E650-60. Epub 2011 Jan 25.
    17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone) exhibits tissue selective anabolic activity: effects on muscle, bone, adiposity, hemoglobin, and prostate.
    Yarrow JF, Conover CF, McCoy SC, Lipinska JA, Santillana CA, Hance JM, Cannady DF, VanPelt TD, Sanchez J, Conrad BP, Pingel JE, Wronski TJ, Borst SE.


    Selective androgen receptor modulators (SARMs) now under development can protect against muscle and bone loss without causing prostate growth or polycythemia. 17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone), a potent testosterone analog, may have SARM-like actions because, unlike testosterone, trenbolone does not undergo tissue-specific 5α-reduction to form more potent androgens. We tested the hypothesis that trenbolone-enanthate (TREN) might prevent orchiectomy-induced losses in muscle and bone and visceral fat accumulation without increasing prostate mass or resulting in adverse hemoglobin elevations. Male F344 rats aged 3 mo underwent orchiectomy or remained intact and were administered graded doses of TREN, supraphysiological testosterone-enanthate, or vehicle for 29 days. In both intact and orchiectomized animals, all TREN doses and supraphysiological testosterone-enanthate augmented androgen-sensitive levator ani/bulbocavernosus muscle mass by 35-40% above shams (P ≤ 0.001) and produced a dose-dependent partial protection against orchiectomy-induced total and trabecular bone mineral density losses (P < 0.05) and visceral fat accumulation (P < 0.05). The lowest doses of TREN successfully maintained prostate mass and hemoglobin concentrations at sham levels in both intact and orchiectomized animals, whereas supraphysiological testosterone-enanthate and high-dose TREN elevated prostate mass by 84 and 68%, respectively (P < 0.01). In summary, low-dose administration of the non-5α-reducible androgen TREN maintains prostate mass and hemoglobin concentrations near the level of shams while producing potent myotrophic actions in skeletal muscle and partial protection against orchiectomy-induced bone loss and visceral fat accumulation. Our findings indicate that TREN has advantages over supraphysiological testosterone and supports the need for future preclinical studies examining the viability of TREN as an option for androgen replacement therapy.

    PMID: 21266670
    The prohormone 19-norandrostenedione displays selective androgen receptor modulator (SARM) like properties after subcutaneous administration.
    Diel P, Friedel A, Geyer H, Kamber M, Laudenbach-Leschowsky U, Schänzer W, Schleipen B, Thevis M, Vollmer G, Zierau O.
    Source

    One of the most frequently misused steroid precursors (prohormones) is 19-norandrostenedione (4-estrene-3,17-dione, NOR), which is, after oral administration, readily metabolised to nortestosterone, also known as nandrolone (durabolin). In this study we have characterised molecular mechanisms of its action determined its tissue specific androgenic and anabolic potency after subcutaneous (s.c.) administration and investigated potential adverse effects. Receptor binding tests demonstrate that NOR binds with high selectivity to the AR. The potency of NOR to transactivate androgen receptor (AR) dependent reporter gene expression was 10 times lower as compared to dihydrotestosterone (DHT). In vivo experiments in orchiectomised rats demonstrated that s.c. treatment with NOR resulted only in a stimulation of the weight of the levator ani muscle; the prostate and seminal vesicle weights remained completely unaffected. Like testosterone, administration of NOR resulted in a stimulation of AR and myostatin mRNA expression in the gastrocnemius muscle. NOR does not affect prostate proliferation, the liver weight and the expression of the tyrosine aminotransferase gene (TAT) in the liver. Summarizing these data it is obvious that NOR, if administrated s.c. and in contrast to its metabolite nandrolone, highly selectively stimulates the growth of the skeletal muscle but has only weak androgenic properties. This observation may have relevance with respect to therapeutic aspects but also doping prevention.

    PMID:18325697
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  12. #72
    ASSFUKKER6969 thefleshlight's Avatar
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    Originally Posted by Dr.Dave1 View Post
    Not recommending it but it's interesting to me that there are studies considering the possible use of Tren and 19-Nor in the realm of SARMS
    Well, enjoy taking tren solo buddy.
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    Originally Posted by thefleshlight View Post
    Well, enjoy taking tren solo buddy.
    Nah, steroids aren't my cup of tea, I think I'll pass
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    Originally Posted by Dr.Dave1 View Post
    Nah, steroids aren't my cup of tea, I think I'll pass
    I'm just stating relative fact I suppose....

    go ahead and use tren solo and we'll see how much you love life being on a "sarm"
    PS- what is the sort of lateral scale for rats to humans again? I forgot; I thought it was something like 5 or 15x's the dose, no? Just curious as to what the roughly estimated human dose of tren would be, for lols.
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    Originally Posted by thefleshlight View Post
    I'm just stating relative fact I suppose....

    go ahead and use tren solo and we'll see how much you love life being on a "sarm"
    PS- what is the sort of lateral scale for rats to humans again? I forgot; I thought it was something like 5 or 15x's the dose, no? Just curious as to what the roughly estimated human dose of tren would be, for lols.
    I like the idea of a SARM being "safer" but there are trade offs; I definitely am very far from being an expert in steroids and I am not advocating the use of any of the drugs for anyone. I just find it interesting.

    Human Equivalent Dosing

    The Human equivalent dosing (mg/kg) = animal dose (mg/kg) x (animal km/human km)
    the km factor will vary based on height and weight of an individual but equals weight in kilos / body surface area (m^2)

    Generally utilized kms for humans 37 and rat = 6. So H.E.D is ~6.2

    I attached an article that has the kms for other animals listed as well
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  16. #76
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    Originally Posted by Dr.Dave1 View Post
    I like the idea of a SARM being "safer" but there are trade offs; I definitely am very far from being an expert in steroids and I am not advocating the use of any of the drugs for anyone. I just find it interesting.
    Well I do and I would comment that if someone ever thought of using tren solo then they would be goddamn crazy. Unfortunately, your abstract doesn't show doses so I'll get the full paper later today and see what that translates to human doses. I certainly hope it's far under 25mg a day for something like tren-e....
    Official Supp. Misc Beer Policeman

    Fancy a hook to your gabber m8?

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