Bill, I looked up the study that you and Cy mentioned on the myotrophic potency of Androst-1-ene and I also looked up a study Brock mentioned in his review of 1-AD. “Anabolic Agents. A-Ring Conjugated Enone Androstane Derivatives”, J. Med. Chem., 8 (1965, 48-51)." This study showed about the same results as the first study as far as Androst-1-ene and its anabolic potency compared to testosterone. However, the thing that I found interesting was that the 17-methylated form of Androst-1-ene was 16 TIMES MORE MYOTROPHIC THAN Methyl-Testosterone with the same androgenic effect! Is it just me or are these results phenomenal? Bill, why did no one ever come out with a Methyl-Androst-1-ene? With its anabolic to androgenic ratio and its inability to interact with aromatase and 5-alpha reductase, it would seem like an awesome steroid. I know that your ethylcarbonate ester for A1E is a great delivery system but would there be any validity to a methyl-A1, even though it may impart some liver toxicity?
I agree with you, methyl-A1 is a very interesting compound that quite possibly could be very worthwhile. If someone, for example GAC, wished to try his hand at it that would be a worthwhile thing to try.
As to why a pharmaceutical company never did it, well, there are very many interesting androgens that never did make it to market. For some reason this one either never got particular attention – perhaps one pharmaceutical company patented it, I don’t know, and then decided they didn’t want to bother with androgens at all, and then no one else wanted it, just to make up one possibility – or perhaps it was tried but did not seem so good once actually tried on man.
It’s the norm, by the way, for compounds not affected by 5alpha-reductase to show much higher ratio of myotrophic (or more precisely, myotrophic on the levator ani of the rat) to “androgenic” (more precisely, hypertrophic on the prostate of the rat) activity than testosterone or methyltestosterone does.
I wouldn’t consider methyl-A1 to be legal
as a dietary supplement.
Esters of naturally occurring substances,
e.g. A1-E, are legal, but when you methylate
you’re definitely making a different, synthetic compound that doesn’t convert
in the body to any natural compound, and it would have to, I think, be considered a new drug. Unless it so happened that it had been present in food prior to DSHEA, but it seems impossible it would have been.
Bill, what is it that makes the ethylcarbonate ester better than other esters for improving steroid clearance of the liver? I found a study on Prednicarbate, the ethylcarbonate form of prednisolone, and it definitely improved the oral absorption, half-life, and activity of prednisolone for up to 12 hours. I just want to know how the ethylcarbonate ester is different from other esters because most esters are hydrolyzed before they even reach the liver. Thanks again Bill.
Just Bumping my question for Bill up.
The body has esterase enzymes that are
“designed” or evolved to be efficient at cleaving ordinary esters – that is, those
that have an alkyl group after the carbonyl carbon. The body is very efficient at this,
and for example in the case of steroids,
the esters are typically cleaved prior to absorption. It’s the free steroid that’s actually absorbed. This is why, for example,
testosterone undecanoate (Andriol) shows a duration of action of only hours, whereas an undecanoate ester if absorbed ought to have a duration of action of more than a week.
(Once absorbed, a steroid ester partitions into fat stores for the most part, over 99.9% of it, and while in fat is protected from esterase enzymes, hence the long duration of action in this case, but that doesn’t apply while in the GI tract.)
Carbonate esters are modified from regular esters in having an alkoxy group after the carbonyl carbon rather than an alkyl – in other words, there’s an added oxygen atom between the carbonyl and the alkyl group. This confers both greater chemical stability and enyzmatic stability, allowing absorption of intact steroid ester.