Anabolic Steroids and the Drug Development Pipeline

I am told that articles on steroids are very popular. I guess there is some mystique surrounding chemicals that have the ability to dramatically transform one’s physique in a short period of time under the right conditions. You would think that people would get bored with this stuff after a while though, right? Well, apparently they don’t.

Anyway, here is yet another steroid article. But what am I to write about? I had to think about this for a while and finally I decided to talk about the development of some steroids that you never heard of because they never made it to the market. I guess that by discussing this subject I can make a point about drug development in general that many people do not understand.

You see, most people assume that all the great drugs developed by pharmaceutical companies must have ended up being sold to the public. If you develop a potent drug that has a good safety profile than naturally you gotta sell it, right? Well, that is not quite right at all. In fact, if you talk to pharmaceutical researchers they will tell you that only a very minor percentage of drugs that show great promise in the lab and/or clinical setting ever make it to market. The reasons for this can be many fold – a crowded market place, patent protection issues, prohibitively high cost of production, or lack of categorical sales can be a few. With the cost of getting a drug approved by the FDA for sale in the millions of dollars, as well as the high cost of drug marketing, you can see that some serious picking and choosing has to go on . The result is many very potent and promising drugs – anabolic steroids in this instance – falling through the cracks and never seeing the pharmacy shelves.

Research and Development of anabolic steroids

For you to fully appreciate the things I am going to discuss in this article you have to have a background on how anabolic steroids are screened for activity. As you know, anabolic steroids are derivatives of testosterone which share two types of activity – muscle building (deemed anabolic) and non muscle male sex hormone related activity (deemed androgenic).

The goal of researchers in the golden age of anabolic steroid research (1935-1965) was to synthesize a compound which retained a high degree of anabolic activity coupled with a vastly diminished androgenic activity. This property was quantified using what is known as the Anabolic / Androgenic ratio (A/A ratio).The goal was not so much to produce a compound that was strongly anabolic, but rather the goal was to produce a compound with the highest possible A/A ratio. You must understand that the market for anabolic steroids was not bodybuilders / athletes but geriatric patients, patients recovering from surgery or injury, or those suffering from weakness or catabolism secondary to some other disease. These can include men and women, and even children. It was therefore paramount to avoid any virilizing effects when providing such people anabolic treatment, and so an anabolic agent with a very low A/A ratio was needed.

To determine the A/A ratio, scientists utilized a test called the Rat Levator Ani Assay. In this test, scientists use two groups of castrated rats. The rats are castrated to remove any interfering influence from fluctuating natural androgen levels. The first group of rats are a control group that receives a placebo, while the second group receives the steroid (either by injection or orally). After a period of time (several days to weeks) the rats are sacrificed. Researchers then isolate three organs from each of the rats – the seminal vesicles, ventral prostate, and levator ani muscle. These organs are all weighed and a comparison of the active group to the placebo groups is made. The differences in weights for the seminal vesicles and ventral prostate represent androgenic activity, while the difference in the weight of the levator ani muscles in the control and active group represent anabolic activity.

To give a landmark against which to gauge the relative activities of each steroid in this assay, a standard is used in some of the rats in the active group. This standard is usually testosterone, testosterone propionate, or 17alpha-methyltestosterone (MT) and the results obtained from the rats given this standard are designated an arbitrary number of 1 for anabolic activity and 1 for androgenic activity. Therefore these standard androgens are said to have an A/A ratio of 1.

Make sense? To tell you the truth I understood this before but I think in the process of writing it down I just confused myself. Anyway, lets look at some steroids.

Some Steroids

Of course out of all the work done during the 30 year heyday of anabolic steroid research came many wonderful compounds. Nandrolone was found to be a steroid with anabolic potency comparable to testosterone but with substantially diminished androgenic activity. Stanozolol (Winstrol) was found to be an orally active androgen with enhanced anabolic activity and reduced androgenic activity relative to MT. Methenolone (Primobolan) on the other hand had slightly diminished anabolic acitivity compared to testosterone, but due to its ultra-low androgenic activity possessed a very favorable A/A ratio. It also was found to be orally active.

As I said before there are many great drugs that never made it to market and there are several possible reasons why these fell through the cracks. In the case of anabolic steroids specifically there are many powerful anabolics that simply did not have a favorable enough A/A ratio. In other words, they were too androgenic. This obviously is of little concern to male bodybuilders and athletes, but for doctors and patients in the clinical settings for which they were developed too much androgenic activity is a definite no-no.

The following are several “lost” steroids. Some of them are very powerful anabolics with bad A/A ratios, but some of them are actually both very potent and have very good ratios. The toxicity of these are unfortunately largely unknown, but a good rule of thumb is the more androgenic and anabolic the more liver toxic.

The Big

Following are some compounds which have anabolic activity that rival many of the most potent anabolic compounds available in pharmacies across the world.

This is a steroid developed by Germans (I assume the infamous East German pharmaceutical company Jenapharm). There has to be something wrong with the numbers in the research because this purportedly has an A/A ratio of something like 121!! The specific numbers say that it has anabolic activity 7.3 times that of methandrostenolone (dianabol) while maintaining a seminal vesicle androgenic reading of 0.06 times that of methandrostenolone. I dunno…….

You steroid chemists out there will notice that this odd steroid is a sort of hybrid between trenbolone acetate and oxandrolone (anavar). The result is that it shares the same low A/A ratio of nandrolone while being 5 times as potent. Probably very expensive to manufacture though.

This orally active compound is a nandrolone derived compound with an 11beta-hydroxyl functional group. This functional group is usually not found on androgens but rather is a key characterisitic of glucocorticoids. In this case it does not seem to hurt the activity of this compound as it measures out with an anabolic activity 8.00 times and an androgenic activity of 2.60 that of MT. The A/A ratio is therefore a fair 3.07

The Bad

These bad boys are at least as strong if not stronger than anything you could ever get your hands on.

You 1-AD aficionados may find this compound vaguely familiar. It is basically a methylated version of 1-testosterone. No, it is not legal for sale as a supplement. Yes, it is very potent – 9.1 to 16.0 times as anabolic as MT. It is mildly androgenic too – 1.0 to 2.2 times MT.

This compound was shown to be 10 times as anabolic as MT orally. By injection however it was only 1.3 times as anabolic. Don’t ask me to explain why. It is also somewhat androgenic – around 3 times as much as MT.

Look familiar? Its almost the same as the previous compound except there is an ethyl group coming off of carbon 13 in the steroid nucleus instead of the normal methyl group. This class of steroids is known as 13beta-ethyl gonanes.The 17alpha methyl is also replaced by an ethyl. The result of these alterations is a significant increase of the anabolic activity. The activity of this compound was compared to 17alpha-ethyl nortestosterone (a strange choice for a standard) and its anabolic potency was 14.5 times this standard. The androgenic activity was reduced to 0.86 the standard.

The Ugly

These compounds serve no practical purpose other than to strike fear into your liver.

This compound actually was sold as a drug at one time and is still used as a standard in in-vitro assays of androgens. It is an oral form of trenbolone basically and it was removed from the market because it had an unacceptable risk of hepatotoxicity. It is extremely anabolic – 120 to 300 times as anabolic compared to MT. It is also very androgenic – around 75 times that of MT. This is obviously not something that you should take without knowing what you are doing. On second thought, this is probably something you should not take at all.

Some sick scientist from Ciba thought that the preceding compound was not strong enough so he slapped a 7alpha-methyl group on it and came up with this monstrosity. Depending on the source it is either 100 times as anabolic as MT or – according to Ciba – 1000 times as anabolic as methandrostenolone (Dianabol). You have to laugh I guess.

Also from Ciba comes this mega-monster steroid. The only data I have on it is that it is 1000 times as potent as MT. I don’t know why Ciba thought it necessary to synthesize things like this because they obviously have no market potential. Just looking at the structure makes my liver ache.

Summary

You just looked at some pretty potent anabolic steroids but don’t get the wrong idea. Just because something is 1000 times as potent as d-bol does not mean that it will get you 1000 times as big as d-bol at the same dose. No, what it means is that it takes a dose 1/1000^th that of a given dose dbol to get the same result. In fact, if you took d-bol like doses of one of those monster steroids in the Ugly section you probably would not get any gains. You would probably just end up sick.

About the author

Patrick Arnold

Organic chemist

Patrick Arnold, widely considered the "father of prohormones", is an organic chemist known for introducing androstenedione, 1-androstenediol, and methylhexanamine into the dietary supplement market. He became infamous for creating the designer steroid tetrahydrogestrinone, also known as THG and "the clear".

Arnold manufactured THG, norbolethone and desoxymethyltestosterone (DMT) for athletes in the BALCO doping scandal. The designer steroids, which were legal at the time of their creation, were difficult for anti-doping authorities to detect.