I appreciate your response,
Olympus Labs. I think, we are all respectul here, aren't we?
The effect of PH/DS is more or less possible to assess because of their chemical structure. They are basing on the cholesterole structure whereas all of the (known) SARM have its own (S4 and Ostarine has similarities because Ostarine is full based on Bicalutamide and S4 only partially). And here is the big problem: we (all, even the researcher) have no clue how the discussed stuff is going to work in the human body.
Let me give you a short example: S4 was cancelled for human trials because of the different NAT expression:
Considering the polymorphism in NAT expression, the interaction between M1 and NAT may raise concerns for drug-drug interactions during clinical applications of S4. The observed species differences suggested that interspecies scaling might not be applicable for predicting the metabolism and disposition of S4 in humans.
This means that it is unclear how S4 (and their metabolites) is mined in the human body due to the unpredictable effects of NAT (N-acetyltransferase) of the main degradation product of S4 called M1. NAT is an enzyme which plays an important role in drug metabolism. In addition, the researchers of GTx had to find that therefore these results can not be extrapolated to humans, the animal studies and therefore can be used for predicting the effect and the elimination of non-S4. Thus was S4 for clinical trials not suitable and was withdrawn from circulation.
There were probably a few more studies with S4 to the animals but the purposes served to examine this first SARM to effect further. S4 (Andarine) was therefore only the first SARM with actual androgenic effect which has proved on closer examination to be unsuitable for humans. Therefore, it has never been more than the three Phase I studies for Andarine 2003/2004. The 2004 planned Phase II study has been (highly probably) never started.
The problem with M1 is that it affects both the ocular receptor and the heart. In addition, the metabolite M1
can affect the RNA. Here are the DNA information copied (transcription) and this passed by the mRNA. It is now
possible that the M1 the RNA in the eye can damage and the RNA can be passed on erroneous information. So it would be theoretically possible that the known side effects of S4 (night blindness, spots in vision, yellow vision) may be permanent.
Questions arise such as:
- If M1 in humans a negative effect on the (m)RNA has: how much is the number of erroneous information? -> The body is able to repair damaged DNA, but only limited (if I have not right in the head). It will probably arrive at the amount of damage.
- As long as the half-life is of Metabolites M1 in the human body? -> Plays probably also play a role in order to minimize the risk. One would have to speed up the rate of degradation of the metabolites.
- The extent to which the metabolites from S4 transmissible to humans? -> See the quoted text above and link: europepmc(dot)org/articles/pmc2039883
In short: S4 was big questionmark not only in the whole mechanism and the many studies with different results. After all, the transfer of "animal" results to humans is also very questionable (without wanting to play it down).
[oh gosh, that example was long, sorry for that
].
To be honest: I misinterpreted firstly the reason for such a thread. I thought,
yates84 was constructing this thread to give full advice (!) how to abuse these drugs on a closed sticky. I didn't considered the other side - the
controlled abuse of these substances to prevent the abusers life as good as possible. Would be glad if he can add on the starting page a warning instruction.
Good idea and glad to take part on this - finally invented - knowledge-collection-thread.
Yours sincerly
sanmarino