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SARM's -- Could they be legal?

I was re-reading one of Cy’s articles which summarized a study on Selective Androgen Receptor Modules (SARM’s), a non-steroidal compound which binds to the AR. My question is, could companies such as Biotest legally sell such a product under the new law banning PHs? And how close are chemists in developing this for the market?

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Androgens Without the Side Effects!

The second study involves compounds classified as SARM’s (Selective Androgen Receptor Modulators). Essentially, these are nonsteroidal compounds which are designed to be more tissue-selective in terms of their effects. In other words, these are compounds which allow one to experience the positive benefits of using androgens while greatly minimizing unwanted side effects. Sounds good, huh?

Essentially, these compounds exert their effects by binding to the AR (androgen receptor) and acting as agonists just as a steroidal androgen would (although it’s possible there are other mechanisms behind their anabolic effects.) The difference is their tissue-selectivity, i.e., being able to activate the androgen receptor in skeletal muscle while not interacting greatly with androgen receptors located in other tissues.

This study and others are allowing us ? Biotest ? to come closer and closer to developing a compound whose anabolic activity greatly exceeds its androgenic side effects that you could use a small enough dose to experience the anabolic effects of the compound and not any of the androgenic side effects. This is why studies evaluating these compounds’ structure-activity relationship (SAR) are so important.

Here’s some additional data from one recent study. Researchers evaluated the anabolic activity of a few of these compounds as compared to Testosterone propionate in rats. One compound was found to be anabolic at a dose of only 0.3 mg/day. Yet, at this same dosage, it had no effect on LH or FSH and nearly zero effect on the prostate and seminal vesicle!

So, with this compound at least, we’ve got anabolic activity which is equal to or greater than Testosterone, with no suppression of LH or FSH and nearly no effect on the seminal vesicle and prostate. While this is great news, there’s still more research to be done before we can reach the point where we actually have a compound which is many times more anabolic than “T,” yet has no effect on LH, FSH, the prostate, etc.

As I said previously, these studies tend to tie in to one another in some way or another. Well, with these compounds, it’s possible we could have one designed which is purely anabolic and activates satellite cells while having zero (or very close to zero) androgenic side effects. Long story short: worries about blood lipids, BPH, alopecia (hair loss) etc., will be greatly minimized or nonexistent. (6-8) And that’s the way, uh huh uh huh, we like it!

Testosterone: Dose and Concentration Dependent

This last study involves developing a method of predicting the anabolic response in men administered androgens, or in this specific case, Testosterone. Just like the first study, this one was a double blind, randomized study consisting of 61 eugonadal men between the ages of 18 and 35. Subjects were again randomly assigned to one of five groups which were administered 25, 50, 125, 300, and 600 mg/weekly for a period of twenty weeks. Again, this was after they had received a GnRH agonist in order to suppress endogenous Testosterone production.

Essentially, what researchers found was that the dose of Testosterone administered could account for 61 to 65% of the variability in terms of anabolic effects. Age and PSA (Prostate-Specific Antigen) could only explain an additional 3 to 5% variance in terms of anabolic effects. Also of note is that that both free and total Testosterone accounted for 32 to 39% of the variance in terms of anabolic effects. In the end, they found that dose and age were the only two consistent predictors.

The serum Testosterone levels, while important, aren’t really a predictor themselves since they’re a function of the Testosterone dose employed. So, essentially, you have the dose of Testosterone being the main determinant of the anabolic response in humans. Age appears to have a small role (i.e, 2-5%) so that leaves room for some other possible predictors, which are really up to speculation.

I’m sure the first response from everyone is, “It’s genetics” and yes, while that blanket statement will suffice, it’s hard to say what the next most important variable would be, perhaps glucocorticoid receptor content, IGF-1 secretion and/or IGF-1 receptor content, myostatin, androgen-receptor content, etc. Nonetheless, this and other data support the idea that the effects on LBM, fat mass, muscle volume (thigh and quadriceps), strength, leg power, hemoglobin, serum IGF-1 and HDL are all dose and concentration-dependent.

The next question is, at what point is this no longer true? Well, it appears that at a dosage of 600 mg/week of Testosterone enanthate, these effects are still dose and concentration dependent. Beyond that, it’s hard to say at what dose exactly this is no longer true. While there is of course a point where these effects are no longer dose-dependent, I’d venture a guess that, in most people, once you’ve gone over 1,000 mg/week the effects are likely no longer dose-dependent. It’s pretty rare for these researchers to exceed 600 mg/week so that question may remain unanswered.

I think this also provides further support for the idea that it’s unnecessary for one to “work his way up” (pyramiding) in terms of dosages when it comes to anabolic steroid use. (9,10)

[quote]TommyRewind wrote:
I was re-reading one of Cy’s articles which summarized a study on Selective Androgen Receptor Modules (SARM’s), a non-steroidal compound which binds to the AR. My question is, could companies such as Biotest legally sell such a product under the new law banning PHs? And how close are chemists in developing this for the market?

=============

www.t-nation.com/readTopic.do?id=459545

Androgens Without the Side Effects!

The second study involves compounds classified as SARM’s (Selective Androgen Receptor Modulators). Essentially, these are nonsteroidal compounds which are designed to be more tissue-selective in terms of their effects. In other words, these are compounds which allow one to experience the positive benefits of using androgens while greatly minimizing unwanted side effects. Sounds good, huh?

Essentially, these compounds exert their effects by binding to the AR (androgen receptor) and acting as agonists just as a steroidal androgen would (although it’s possible there are other mechanisms behind their anabolic effects.) The difference is their tissue-selectivity, i.e., being able to activate the androgen receptor in skeletal muscle while not interacting greatly with androgen receptors located in other tissues.

This study and others are allowing us ? Biotest ? to come closer and closer to developing a compound whose anabolic activity greatly exceeds its androgenic side effects that you could use a small enough dose to experience the anabolic effects of the compound and not any of the androgenic side effects. This is why studies evaluating these compounds’ structure-activity relationship (SAR) are so important.

Here’s some additional data from one recent study. Researchers evaluated the anabolic activity of a few of these compounds as compared to Testosterone propionate in rats. One compound was found to be anabolic at a dose of only 0.3 mg/day. Yet, at this same dosage, it had no effect on LH or FSH and nearly zero effect on the prostate and seminal vesicle!

So, with this compound at least, we’ve got anabolic activity which is equal to or greater than Testosterone, with no suppression of LH or FSH and nearly no effect on the seminal vesicle and prostate. While this is great news, there’s still more research to be done before we can reach the point where we actually have a compound which is many times more anabolic than “T,” yet has no effect on LH, FSH, the prostate, etc.

As I said previously, these studies tend to tie in to one another in some way or another. Well, with these compounds, it’s possible we could have one designed which is purely anabolic and activates satellite cells while having zero (or very close to zero) androgenic side effects. Long story short: worries about blood lipids, BPH, alopecia (hair loss) etc., will be greatly minimized or nonexistent. (6-8) And that’s the way, uh huh uh huh, we like it!

Testosterone: Dose and Concentration Dependent

This last study involves developing a method of predicting the anabolic response in men administered androgens, or in this specific case, Testosterone. Just like the first study, this one was a double blind, randomized study consisting of 61 eugonadal men between the ages of 18 and 35. Subjects were again randomly assigned to one of five groups which were administered 25, 50, 125, 300, and 600 mg/weekly for a period of twenty weeks. Again, this was after they had received a GnRH agonist in order to suppress endogenous Testosterone production.

Essentially, what researchers found was that the dose of Testosterone administered could account for 61 to 65% of the variability in terms of anabolic effects. Age and PSA (Prostate-Specific Antigen) could only explain an additional 3 to 5% variance in terms of anabolic effects. Also of note is that that both free and total Testosterone accounted for 32 to 39% of the variance in terms of anabolic effects. In the end, they found that dose and age were the only two consistent predictors.

The serum Testosterone levels, while important, aren’t really a predictor themselves since they’re a function of the Testosterone dose employed. So, essentially, you have the dose of Testosterone being the main determinant of the anabolic response in humans. Age appears to have a small role (i.e, 2-5%) so that leaves room for some other possible predictors, which are really up to speculation.

I’m sure the first response from everyone is, “It’s genetics” and yes, while that blanket statement will suffice, it’s hard to say what the next most important variable would be, perhaps glucocorticoid receptor content, IGF-1 secretion and/or IGF-1 receptor content, myostatin, androgen-receptor content, etc. Nonetheless, this and other data support the idea that the effects on LBM, fat mass, muscle volume (thigh and quadriceps), strength, leg power, hemoglobin, serum IGF-1 and HDL are all dose and concentration-dependent.

The next question is, at what point is this no longer true? Well, it appears that at a dosage of 600 mg/week of Testosterone enanthate, these effects are still dose and concentration dependent. Beyond that, it’s hard to say at what dose exactly this is no longer true. While there is of course a point where these effects are no longer dose-dependent, I’d venture a guess that, in most people, once you’ve gone over 1,000 mg/week the effects are likely no longer dose-dependent. It’s pretty rare for these researchers to exceed 600 mg/week so that question may remain unanswered.

I think this also provides further support for the idea that it’s unnecessary for one to “work his way up” (pyramiding) in terms of dosages when it comes to anabolic steroid use. (9,10)[/quote]

Well, these are not steroid molecules and there are some naturally occurring compounds which may have some activity. There are some molecules from a certain type of marine algae but they would have to be altered in order to have a SARM. However, doing so is most certainly not an easy, nor inexpensive task.

As for how close SARM’s are to being on the market, not very close. They’ve recently started Phase I trials on one SARM in particular. Everything else I’ve seen thus far as been in animal models and it seems they’ve only recently narrowed it down to a few molecules which are best suited for particular uses. I would guesstimate that it’s going to be at least a number of years before you’ll see anything.

As an interesting side note, I had a friend who was working as a research tech at the lab/company which is in development of these compounds and related compounds, back when they were still researching the effects in animals. I often joked that he should accidentally wind up with the data in his hand as he walked out one day. Unfortunately, they wouldn’t even tell him what the compound was for, let alone the developmental name and of course not the structure.

Oh, and as for how these will be classified. Well, technically speaking, they should be placed in the same category as SERM’s, but I’m almost certain they’ll be schedule III drugs.

Thanks a lot for the reply and the reality check. It was good of you to discuss some inside info too. I’ve checked out some other boards and some people are getting a little excited about how these will replace PHs.