If women can have SERMs men can have SARMs

[Dr.Dave1]

1: J Steroid Biochem Mol Biol. 2008 Apr 20. [Epub ahead of print] Links
A selective androgen receptor modulator with minimal prostate hypertrophic activity restores lean body mass in aged orchidectomized male rats.
Allan G, Sbriscia T, Linton O, Lai MT, Haynes-Johnson D, Bhattacharjee S, Ng R, Sui Z, Lundeen S.

Androgens are required for the maintenance of normal sexual activity in adulthood and for enhancing muscle growth and lean body mass in adolescents and adults. Androgen receptor (AR) ligands with tissue selectivity (selective androgen receptor modulators, or SARMs) have potential for treating muscle wasting, hypogonadism of aging, osteoporosis, female sexual dysfunction, and other indications. JNJ-37654032 is a nonsteroidal AR ligand with mixed agonist and antagonist activity in androgen-responsive cell-based assays. It is an orally active SARM with muscle selectivity in orchidectomized rat models. It stimulated growth of the levator ani muscle with ED(50) 0.8mg/kg, stimulating maximal growth at a dose of 3mg/kg. In contrast, it stimulated ventral prostate growth to 21% of its full size at 3mg/kg. At the same time, [b]JNJ-37654032 reduced prostate weight in intact rats by 47% at 3mg/kg, while having no inhibitory effect on JNJ-37654032 restored about 20% of the lean body mass lost following orchidectomy in aged rats. JNJ-37654032 reduced follicle-stimulating hormone levels in orchidectomized rats and reduced testis size in intact rats. JNJ-37654032 is a potent prostate-sparing SARM with the potential for clinical benefit in muscle-wasting diseases.

PMID: 18502117 [PubMed - as supplied by publisher]

interesting results on the orchiectomized rats although the results on the "intact" rat's muscle mass is not mind blowing

[BigDude22s]

Trash.

SARMs are trash and I will tell you why.

Hormones have many interactions outside of the androgen receptor.

For example dbol barely binds to the androgen receptor, it exerts its effects through unknown means.

I have no clue what SARMs could be a replacement for, but certainly not a replacement for steroids of any kind.

you heard it here first, SARMs will have zero function in humans for maintaining or gaining lean muscle mass. You supplement idiots have no idea about steroids.

[Dr.Dave1]

Trash.

SARMs are trash and I will tell you why.

Hormones have many interactions outside of the androgen receptor.

For example dbol barely binds to the androgen receptor, it exerts its effects through unknown means.

I have no clue what SARMs could be a replacement for, but certainly not a replacement for steroids of any kind.

you heard it here first, SARMs will have zero function in humans for maintaining or gaining lean muscle mass. You supplement idiots have no idea about steroids.

If you have any science to back your claims go for it

[BigDude22s]

If you have any science to back your claims go for it

We dont do science here, just raw brotelligence telling it like it is.

SARMs will never be a replacement for steroids.

dbol having 90% of its activity outside the AR is proof enough. This is a well known fact, and I don't need to say any more.

Just based on the dbol example, SARMs can't replace steroids.

The androgen receptor is not the end-all of growth. Far from it actually.

[Dr.Dave1]

We dont do science here, just raw brotelligence telling it like it is.

SARMs will never be a replacement for steroids.

dbol having 90% of its activity outside the AR is proof enough. This is a well known fact, and I don't need to say any more.

Just based on the dbol example, SARMs can't replace steroids.

The androgen receptor is not the end-all of growth. Far from it actually.

actually in this section we rely on science . . . people use broscience when they know they can't back up their claims. I do not remember mentioning they would replace steroids (although it is a possibility), SARMs seem to have potential and are likely to have less side effects

I'm not sure how you can shoot down SARMs when true SARMs have not even been produced by the pharmas for human use. The compounds in the lab have varying strengths/affinitys. I think it will be interesting to see how it pans out. However, it's a free world; feel free believe what ya like

[BigDude22s]

actually in this section we rely on science . . . people use broscience when they know they can't back up their claims. I do not remember mentioning they would replace steroids (although it is a possibility), SARMs seem to have potential and are likely to have less side effects

I'm not sure how you can shoot down SARMs when true SARMs have not even been produced by the pharmas for human use. The compounds in the lab have varying strengths/affinitys. I think it will be interesting to see how it pans out. However, it's a free world; feel free believe what ya like

I think SARMs will be for sex drive/ erectile issues and perhaps some strength/preservation of muscle.

I can see SARMs being like a better version of proviron.

They will however be a poor mass builder. Anadrol is another example of a steroid with almost no affinity for the AR.

We will see, its not long before some compounds are officially cleared for research and start popping up on some sites.

[Dr.Dave1]

an article on a new way to target sarms so that they only affect skeletal muscles instead of other tissues with androgen receptors . . . seems to have promise

1: J Steroid Biochem Mol Biol. 2008 Sep;111(3-5):157-63. Epub 2008 Jun 11. Links
[/b]Actin associated proteins function as androgen receptor coregulators: An implication of androgen receptor's roles in skeletal muscle.[/b]
Ting HJ, Chang C.

This review of androgen receptor (AR) coregulators, which also function as actin-binding proteins, intends to establish the connection between actin cytoskeletal components and androgen signaling, especially in skeletal muscle. In cellular and animal models, androgen activated AR modulates myoblasts proliferation, promotes sexual dimorphic muscle development, and alters muscle fiber type. In the clinical setting, administration of anabolic androgens can decrease cachexia and speed wound healing. During myogenesis and regeneration of skeletal muscle in embryo and adult, the membrane of myoblasts fuse and the actin cytoskeleton is rearranged to form an alignment with myosin to form myotubes then ultimately the myofibrils. Contraction of skeletal muscle promotes the growth of myocytes by coordinating signals from the neuromuscular junction to intra-myofibrils through costameres, the functional structure comprised of signal proteins closely associated with actin filaments and involved in muscular dystrophy. Therefore, the discovery of actin-binding proteins functioning as AR coregulators implies that androgen signaling is tightly regulated during the process of the development and regeneration of skeletal muscle. The search for selective androgen receptor modulators (SARM) that act precisely in skeletal muscle instead of other tissues could target the engineering of a SARM-AR complex that selectively recruits these coregulators.

PMID: 18590822 [PubMed - in process]

[Dr.Dave1]

another rat study with promise as a male contraceptive

1: Endocrinology. 2008 Sep 4. [Epub ahead of print] Links
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.
Jones A, Chen J, Hwang DJ, Miller DD, Dalton JT.


The pharmacologic effects of (S)-N-(4-Cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro, 4-chlorophenoxy)-2-Hydroxy-2-Methyl-Propanamide (S-23) were characterized in male rats as an animal model of hormonal male contraception. S-23 showed high binding affinity (Ki=1.7+/-0.2 nM) and was identified as a full agonist in vitro. In castrated male rats, the ED50 of S-23 in the prostate and levator ani muscle was 0.43 and 0.079 mg/day, respectively. In intact male rats treated for 14 days, S-23 alone suppressed LH levels by greater than 50% at doses greater than 0.1 mg/day, with corresponding decreases in the size of the prostate but increases in the size of levator ani muscle. In intact male rats treated for up to 10 weeks with S-23 and estradiol benzoate (EB; necessary to maintain sexual behavior in rats), S-23 showed biphasic effects on androgenic tissues and spermatogenesis by suppressing serum concentrations of luteinizing hormone and follicle stimulating hormone. EB alone showed no effect on spermatogenesis. In the EB + S-23 (0.1mg/day) group, 4/6 of animals showed no sperm in the testis and zero pregnancies (0/6) in mating trials. After termination of treatment, infertility was fully reversible, with a 100% pregnancy rate observed after 100 days of recovery. S-23 increased bone mineral density and lean mass, but reduced fat mass in a dose-dependent manner. This is the first study to show that a SARM combined with EB is an effective and reversible regimen for hormonal male contraception in rats. The beneficial effects of S-23 on the muscle, tissue selectivity, and favorable pharmacokinetic properties make it a strong candidate for use in oral male contraception.

PMID: 18772237 [PubMed - as supplied by publisher]

a loo at the pathways involved

1: Mol Endocrinol. 2008 Sep 18. [Epub ahead of print] Links
Steroidal Androgens and Nonsteroidal, Tissue Selective Androgen Receptor Modulators (SARM), S-22, Regulate Androgen Receptor Function Through Distinct Genomic and Non-Genomic Signaling Pathways.
Narayanan R, Coss CC, Yepuru M, Kearbey JD, Miller DD, Dalton JT.


Androgen Receptor (AR) ligands are important for the development and function of several tissues and organs. However, the poor oral bioavailability, pharmacokinetic properties, and receptor cross-reactivity of testosterone, coupled with side effects, place limits on its clinical use. SARMs elicit anabolic effects in muscle and bone, sparing reproductive organs like the prostate. However, molecular mechanisms underlying the tissue selectivity remain ambiguous. We performed a variety of in vitro studies to compare and define the molecular mechanisms of an aryl propionamide SARM, S-22, as compared to DHT. Studies indicated that S-22 increased levator ani muscle weight but decreased the size of prostate in rats. Analysis of the upstream intracellular signaling events indicated that S-22 and DHT mediated their actions through distinct pathways. Modulation of these pathways altered the recruitment of AR and its cofactors to the PSA enhancer in a ligand-dependent fashion. In addition, S-22 induced Xenopus laevis oocyte maturation and rapid phosphorylation of several kinases, through pathways distinct from steroids. These studies reveal novel differences in the molecular mechanisms by which S-22, a non-steroidal SARM, and DHT mediate their pharmacologic effects.

PMID: 18801930 [PubMed - as supplied by publisher]

[inhuman warrior]

Alot of useful info in this thead.

[bongd]

So the question begs to be answered, and ask it I shall... has anyone used S-4 or any SARMs out there yet!?!?!?

[IronPimper]

I've heard from some people who have used S-4. Dosages ranged from 50-200mg/day and the feedback from some pretty experienced people was that at 200mg/day it feels like 500mg/test per week. So essentially, you need about 1.5g of this stuff a week to have pretty good results.

[javin86]

I've heard from some people who have used S-4. Dosages ranged from 50-200mg/day and the feedback from some pretty experienced people was that at 200mg/day it feels like 500mg/test per week. So essentially, you need about 1.5g of this stuff a week to have pretty good results.

agreed, there was a thread about it over at olm. The results seem to be good. The rep for the company selling it is recommending it be used in pct though... not sure if that's a good idea.

[bongd]

agreed, there was a thread about it over at olm. The results seem to be good. The rep for the company selling it is recommending it be used in pct though... not sure if that's a good idea.

Why wouldn't it be good for PCT? From what I've read, it should be excellent.

Hmm.. but I will continue to look into this. You can read about things on paper and in real life and they're not always in alignment.

[javin86]

that's pretty much what i ment, that's a specific area I wouldn't want to mess around with.

[Patrick Arnold]

I proposed this idea almost a year ago to a research chem company to produce SARMs (*I thought it would be legal to sell as a research chem like SERMs). then about half a year ago, I worked with another chem company on the feasibility of coming out with some SARMs....we went so far as to identify which one(s) would be the best to produce. Eventually, the product was scrapped, for various reasons.
.

this guy cannot be serious

[Patrick Arnold]

I actually wasn't going to make any money off the idea, and I wasn't asking for co-operation. I just proposed it to them as an idea they may be interested in going with. I don't make any money from the sale of research chems nor would I be interested in doing so.

Also, I believe that the end issue wasn't that they didn't want to produce the SARMs, but rather that there was an issue sourcing it. So they didn't refuse to co-operate, per se, but just were unable to follow through with my idea.

It doesn't concern me one way or another, because as I said, I wasn't going to make anything from it...I just proposed it as something that may have interested them (I sent them a bunch of data on it).

your initial post had me confused. i guess what you meant is that you wanted some chemical company to make one of the SARMs whose synthesis and pharmacological activity has already been documented

it sounded initially that you were developing your own novel molecules.

[Patrick Arnold]

Some great questions Dr.P and while I am far from an expert in endocrinology I can answer to the best of my ability based on what was said in the articles. Anyone else is more than welcome to add their two cents.

As for affecting the HPTA - yes. All of the compounds that I read about decreased blood LH level (which would lead to a decrease in Testosterone production). In fact one of the compounds S-3 was being investigated to be used as a male contraceptive (using the feedback to decrease spermatogenesis). However, the level at which they affect the HTPA is variable. For example compound BMS-564929 had a 9 fold selectivity for muscle stimulation vs LH suppression, which can be compared to testosterones 1.2 fold selectivity (aka no selectivity) for muscle stimulation vs LH suppression. You also have to take into account that they are utlizing castrated rats . . . the effect in humans is yet to be seen.
(7R,7aS)-10b had a >50 fold selectivity for muscle vs prostate and a 30 fold selectivity for muslce vs LH suppression. However this compound is in earlier stages of development but looks great so far

you should take into account also that this selectivity is probably highly dose dependent

a granma dose might have good selectivity while a bodybuilder dose might not

[IronPimper]

Why wouldn't it be good for PCT? From what I've read, it should be excellent.

Hmm.. but I will continue to look into this. You can read about things on paper and in real life and they're not always in alignment.

I believe the main concern is that even though these sarms don't have (at least they do not seem to have) the same negative effects on the body, they still have an effect on the hpta to varying degrees. And as PA mentioned, a bbers dose could strongly impact the hpta.

I believe these sarms, if ever available, have the most potential as a bridge between a cycle, or as a cycle of their own after pct from a previous cycle.

For example:

Test Ent. 500mg/wk for 10 weeks
S-4: 200mg/day for 6 weeks
Test Ent. 500mg/wk for 10 weeks

or

Test Ent. 500mg/wk for 10 weeks
PCt for 4 weeks
S-4 for 4-6 weeks

[Patrick Arnold]

I've heard from some people who have used S-4. Dosages ranged from 50-200mg/day and the feedback from some pretty experienced people was that at 200mg/day it feels like 500mg/test per week. So essentially, you need about 1.5g of this stuff a week to have pretty good results.

down the street from me there is a custom synthesis place that makes SARMS for testing for pharm companies (i dunno if its just one pharm company or more then one)

according to a guy that works there they have made dozens of them. many ones that were active and good were discarded though because the pharm company wants ones that are active at very small doses. that is so they make more money and also because of ease of formulating

whatever this S-4 is it cannot be a candidate for further development if its active dose is as high as you say

[Patrick Arnold]

I've heard from some people who have used S-4. Dosages ranged from 50-200mg/day and the feedback from some pretty experienced people was that at 200mg/day it feels like 500mg/test per week. So essentially, you need about 1.5g of this stuff a week to have pretty good results.

i asked someone to send me some of this so i could test. he asked his supplier and the supplier got very angry at him. i have a suspicion that this stuff may just be an anabolic steroid

SARMs are very hard to synthesize. expensive. so either people are shelling out a boatload of money for a cycle of the stuff or is bunk (perhaps just trenbolone acetate or something)

is S-4 same thing as ostarine?

[Black_Label]

That was an intersting read, I need to come by this section more often. Great change from teen section or the stupid questions in supp main

[bobraskin]

That was an intersting read, I need to come by this section more often. Great change from teen section or the stupid questions in supp main

yeah great thread well worth the read

____________________________
Dont be too quick to judge

[bongd]

down the street from me there is a custom synthesis place that makes SARMS for testing for pharm companies (i dunno if its just one pharm company or more then one)

according to a guy that works there they have made dozens of them. many ones that were active and good were discarded though because the pharm company wants ones that are active at very small doses. that is so they make more money and also because of ease of formulating

whatever this S-4 is it cannot be a candidate for further development if its active dose is as high as you say

So I guess this would probably benefit an old dude with low test and a rancid ****ter (prostate) much more than a bodybuilder, eh? I guess the promise of SARMs isn't really there in reality. I knew that it'd probably be too good to be true.

The S-4 SARM shouldn't be ostarine. Not from what I've read at least... I may be mistaken though. All the anecdotal feedback I've heard from everyone on the juicer forums seems to indicate that it's something different and not too exciting, whatever it is.

[Patrick Arnold]

So I guess this would probably benefit an old dude with low test and a rancid ****ter (prostate) much more than a bodybuilder, eh? I guess the promise of SARMs isn't really there in reality. I knew that it'd probably be too good to be true.
(

they may be able to get more separation of anabolic from androgenic than they could with AAS, however like i said when you take large dosages you get a convergence of activities

OTOH they may be able to make a SARM which does not cross the BBB. that could mean anabolism without suppression. However you will get no CNS boost either (not always a big deal though)

[IronPimper]

i asked someone to send me some of this so i could test. he asked his supplier and the supplier got very angry at him. i have a suspicion that this stuff may just be an anabolic steroid

SARMs are very hard to synthesize. expensive. so either people are shelling out a boatload of money for a cycle of the stuff or is bunk (perhaps just trenbolone acetate or something)

is S-4 same thing as ostarine?

GTx hasn't told anyone which sarm ostarine is, though I've heard mention of it being s-1.

One thing that concerns me is the constant mention of vision problems while taking S-4, something that I don't think would have allowed it to pass through phase II testing.

I am guessing Ostarine = S-1, S-4 much more potent than S-1 with significantly more side effects

[Patrick Arnold]

GTx hasn't told anyone which sarm ostarine is, though I've heard mention of it being s-1.

One thing that concerns me is the constant mention of vision problems while taking S-4, something that I don't think would have allowed it to pass through phase II testing.

I am guessing Ostarine = S-1, S-4 much more potent than S-1 with significantly more side effects

S-4 more potent than ostarine? if indeed s-4 requires 100mg a day then it has horrible potency. Ostarine can't be worse than that or it wouldn't be a candidate for market approval


p.s. it wouldn't be hard to figure all this out. you can find out the chemical that s-4 is pretty readilly by looking at the patents. and i am sure ostarine is a known structure if you search

[IronPimper]

S-4 more potent than ostarine? if indeed s-4 requires 100mg a day then it has horrible potency. Ostarine can't be worse than that or it wouldn't be a candidate for market approval


p.s. it wouldn't be hard to figure all this out. you can find out the chemical that s-4 is pretty readilly by looking at the patents. and i am sure ostarine is a known structure if you search

This is S-4:

S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide

I haven't been able to locate the patents on ostarine.

Selective Androgen Receptor Modulator Treatment Improves Muscle Strength and Body Composition and Prevents Bone Loss in Orchidectomized Rats


The partial agonist activity of a selective androgen receptor modulator (SARM) in the prostate was demonstrated in orchidectomized rats. In the current study, we characterized the full agonist activity of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (a structurally related SARM referred to in other publications and hereafter as S-4) in skeletal muscle, bone, and pituitary of castrated male rats. Twelve weeks after castration, animals were treated with S-4 (3 or 10 mg/kg), dihydrotestosterone (DHT) (3 mg/kg), or vehicle for 8 wk. S-4 (3 and 10 mg/kg) restored soleus muscle mass and strength and levator ani muscle mass to that seen in intact animals. Similar changes were also observed in DHT-treated (3 mg/kg) animals. Compared with the anabolic effects observed in muscle, DHT (3 mg/kg) stimulated prostate and seminal vesicle weights moire than 2-fold greater than that observed in intact controls, whereas S-4 (3 mg/kg) returned these androgenic organs to only 16 and 17%, respectively, of the control levels. S-4 (3 and 10 mg/kg) and DHT (3 mg/kg) restored castration-induced loss in lean body mass. Furthermore, S-4 treatment caused a significantly larger increase in total body bone mineral density than DHT. S-4 (3 and 10 mg/kg) also demonstrated agonist activity in the pituitary and significantly decreased plasma LH and FSH levels in castrated animals in a dose-dependent manner. In summary, the strong anabolic effects of S-4 in skeletal muscle, bone, and pituitary were achieved with minimal pharmacologic effect in the prostate. The tissue-selective pharmacologic activity of SARMs provides obvious advantages over steroidal androgen therapy and demonstrates the promising therapeutic utility that this new class of drugs may hold.

[Patrick Arnold]

read up just now on the arylpropionamide SARMs developed by GTX. Apparently S-4 was the first one they made that had in-vivo activity but since then they have made much more potent analogs. Pretty certain that Ostarine would have been one of these later developments.

anyway, my friend that works at the place that makes SARMs down the street can probably give more details

[IronPimper]

read up just now on the arylpropionamide SARMs developed by GTX. Apparently S-4 was the first one they made that had in-vivo activity but since then they have made much more potent analogs. Pretty certain that Ostarine would have been one of these later developments.

anyway, my friend that works at the place that makes SARMs down the street can probably give more details

cool, would love an update if you get any pertinent information

[chuckisnutz]

bump on this, sir.