RU58841, spironolactone, and castration: a direct comparison!!
Bryan Shelton
on RU58841. In fact, it's the very first one by the scientists at
Roussel Uclaf. And after studying it, gosh darn if we don't suddenly
have a pretty reasonable way of making fairly direct comparisons
between RU58841 and topical spironolactone and castration! BTW,
they actually describe the method they used for synthesizing this
stuff, and one of the first steps involves the use of phosgene! Ouch!
I'm gonna ship Russell a supply of these chemicals, including a tank
of phosgene gas, and let HIM mix it up! Russell, email me your
snail-mail address. :-)
Right up front, I'll say that there's some good news and some bad news
for Russell. The *good* news is that I've finally found an RU58841
study that speaks "glowingly" of this drug, and suggests its possible
use in humans for androgen-dependent skin conditions. The *bad* news
is that this drug doesn't really seem to be that huge of an improvement
over topical spironolactone; and the real kicker is that it is NOT as good
as...(drum-roll)... *castration* in these animal studies. Onward to the data:
The study is: "RU58841, A New Specific Topical Antiandrogen: A
Candidate of Choice for the Treatment of Acne, Androgenetic Alopecia
and Hirsutism", T. Battmann et al, J. Steroid Biochem. Molec. Biol., Vol. 48,
No. 1, pp. 55-60, 1994.
They used the standard hamster flank organ test to see the biological
effect of this drug. They applied varying doses of RU58841 in ethanol
to only one flank organ of one group of hamsters, and ethanol only as
a control to another group. A third group was castrated and had ethanol
only applied as another kind of control.
The results: The largest dose of RU58841 that was tested, 0.1 mg,
caused a 52.4% reduction in the flank organ after 3 weeks. But in
comparison, castration caused a rapid decrease of flank organ size
of 51.7% in only 7 days, and reached a plateau of 76.6% in 2 weeks.
This clearly shows that castration produces a powerful reduction in
androgenic activity, and that while RU58841 is a very good topical
antiandrogen, it doesn't quite match castration.
What about spironolactone? Well, we can look at other studies that
tested spiro in a very similar fashion: "Antiandrogenic Effects of
Topically Applied Spironolactone on the Hamster Flank Organ",
Arthur Weissmann et al, Archives of Dermatology, Vol. 121, Jan 1985.
They applied varying doses of spironolactone in isopropyl myristate in
isopropyl alcohol to only one flank organ of a group of hamsters. Another
group got only the vehicle as a control. Still another group was castrated
to serve as a different kind of control.
The results: the 0.3 mg dose of spironolactone caused a 39.3% reduction
in the flank organ after 28 days. But in comparison, castration caused a
reduction of 74.6%.
And here's a bonus factoid: in the study from which I've previously
quoted in my posts about Revivogen, "Growth Suppression of Hamster
Flank Organs by Topical Application of Gamma-Linolenic and Other
Fatty Acid Inhibitors of 5Alpha-Reductase", the application of 2 mg
per day of GLA to one flank organ of pre-pubertal hamsters caused
a suppression of the growth of the pigmented macule of that organ
during maturation of 66%. (Keep in mind that GLA is only a 5AR
blocker, and not an androgen receptor blocker.)
Summing up, the RU58841 suppressed flank organs by 52.4% and
spironolactone (a larger dose, however) suppressed it by 39.3%.
Castration in both of these studies was a consistent 75%. The
bottom line would appear to be that RU58841 does indeed seem
to be a very potent topical antiandrogen. Probably the best.
However, it doesn't seem to me to be *dramatically* beyond what
can be achieved with the careful use of other drugs like spironolactone.
Furthermore, neither one of these drugs achieved the androgen-
reducing effect of castration in this animal model. I think the point
of this is now obvious to everyone: if castration in humans doesn't
cause much regrowth, how much regrowth could we expect from
RU58841?
Bryan
Manelessrjd
>Hey, guys! I was at the library today, and picked up another article
>on RU58841
Boy, you're going through a lot of trouble in this debate. Mike says I'm the
only one that is *intense* in this debate.
I can't really blame you though, you can't have guys thinking antiandrogens
might cure their hair loss. If guys believed the antiandrogens would solve
their problem,
they'd get suspicious of Dr.P.'s *stuff*.
Keep fighting hard Bryan. You gotta keep these guys in the ng thinking that
antiandrogen therapy is not the answer.
Your livlihood's on the line.
BTW you should've just asked me for a copy of the J of Steroidal Biochemistry
with the RU58841 article, I've had it for years.
>And after studying it, gosh darn if we don't suddenly
>have a pretty reasonable way of making fairly direct comparisons
>between RU58841 and topical spironolactone and castration!
Oh I can't wait to see your "pretty reasonable way" to determine RU58841's
efficacy in humans. Goodie goodie, I hope it's more of your quackery
prostate cancer patients stuff.
I know there are no stumptail macaques in that study since I've read it
numerous times so
I can't wait to see what scam you've got for us this time.
>BTW,
>they actually describe the method they used for synthesizing this
>stuff, and one of the first steps involves the use of phosgene! Ouch!
They disable the phosgene gas, fool. You don't need to be fearful. You're a
melodramatic asshole.
BTW last I heard they were using a relative of the AIDS virus to transport the
new & healthy genes into patien'ts bodies when they do genetic engineering,
but they likewise disable that virus transport too.
Do you know how much medicine starts out dangerous, and then they alter it, for
practical use?
>I'm gonna ship Russell a supply of these chemicals, including a tank
>of phosgene gas, and let HIM mix it up! Russell, email me your
>snail-mail address. :-)
>
Why don't you just give it to your *bud* Dr.P., and talk to him about whipping
up RU58841?
BTW Bryan I've known for years that the instructions how to make RU58841 are in
that journal article. T. Battman told me so because
he felt badly for me when Roussel Uclaf, the company he worked for, got bought
up by Hoecsht, and Hoecsht shit canned RU58841.
You should've just told me you didn't have the recipe for RU58841. I've had
the recipe for years.
>The *good* news is that I've finally found an RU58841
>study that speaks "glowingly" of this drug, and suggests its possible
>use in humans for androgen-dependent skin conditions.
There are other studies that speak glowingly of RU58841.
>The *bad* news
>is that this drug doesn't really seem to be that huge of an improvement
>over topical spironolactone;
What a laugh.
> and the real kicker is that it is NOT as good
>as...(drum-roll)... *castration* in these animal studies
What animals? The stumptail macaques right?
Is this the new scam Bryan? aRe you gonna try to compare a rat, or a hamster,
to a human?
LOL.
> The largest dose of RU58841 that was tested, 0.1 mg,
>caused a 52.4% reduction in the flank organ after 3 weeks. But in
>comparison, castration caused a rapid decrease of flank organ size
>of 51.7% in only 7 days, and reached a plateau of 76.6% in 2 weeks
1. This is a small dose. They can just increase the dose, and get more
androgen suppression.
2. You take me to task over the stumptail macaque studies despite the fact
that the entire dermatological community (except for perhaps your bud, Dr.P.)
and the entire parmaceutical industry recognizes the stumptail macaque as the
#1 model for Male Pattern Baldness, And then you wanna compare a hamster flank
organ to a man's hair.
You're a joke.
>This clearly shows that castration produces a powerful reduction in
>androgenic activity, and that while RU58841 is a very good topical
>antiandrogen, it doesn't quite match castration.
>
At that low dose fool. On the flank organ of a *hamster* at a low dose. They
can increase the dose and get better results Mr. slick.
>What about spironolactone? Well, we can look at other studies that
>tested spiro in a very similar fashion: "Antiandrogenic Effects of
>Topically Applied Spironolactone on the Hamster Flank Organ",
>Arthur Weissmann et al, Archives of Dermatology, Vol. 121, Jan 1985.
>
Topical spironolcactone works well on Hamsters and rodents, but it's activity
in human skin applied topically is weak and equivocal.
>
>Summing up, the RU58841 suppressed flank organs by 52.4% and
>spironolactone (a larger dose, however) suppressed it by 39.3%.
>Castration in both of these studies was a consistent 75%
They could've increased the RU58841 dose and gotten better results.
>The
>bottom line would appear to be that RU58841 does indeed seem
>to be a very potent topical antiandrogen. Probably the best.
>However, it doesn't seem to me to be *dramatically* beyond what
>can be achieved with the careful
>use of other drugs like spironolactone.
If you're a hamster.
I'm not.
I'm a guy.
Topical spironolactone's activity in skin applied topically is weak and
equivocal.
RU58841 is highly active in skin.
>Furthermore, neither one of these drugs achieved the androgen-
>reducing effect of castration in this animal model.
Yea, RU58841 was at a low dose, and a hamster flank organ is not a good model
for human MPB.
Hey flake, how come when I wanted to use
hamster flank organs to prove the effectiveness of human hair gorwth with the
presently available antiandrogens you cried foul?
Hey slick, if I you won't let me use the hamster flank organ as an example to
prove human hair growth how come you can?
It's already been agreed that we would accept the stumptail macaque hair growth
studies because of their close similarity to male pattern baldness in a man,
but you wouldn't let me use any other animals, and I accepted that.
Now you wanna change it.
Hey look, slick, are we gonna be using all these antiandrogen studies in
men/women/hamsters/etc or not?
If we are, I can disprove all your crap about the innefectiveness of
antiandrogens with both hands tied behind my back.
The only thing I insist if we are going to use all the antiandrogens in all
these *creatures* is that the route of delivery must be the same.
If one creature took it orally, the other creature must also have taken it
orally for it to count.
and on the issue of RU58841 not doing as well as castrration in this RU58841
study you displayed so proudly read my lips:
THEY COULD HAVE JSUT RAISED THE DOSE OF THE RU58841 AND GOTTEN BETTER RESULTS
FOOL
>I think the point
>of this is now obvious to everyone: if castration in humans doesn't
>cause much regrowth, how much regrowth could we expect from
>RU58841?
>
A lot because castration leaves behind 30 % of a man'sDHT in his body, and
perhaps more up there in the skin of his scalp.
On the other hand, the dose of RU58841 can be increased and you can get rid of
*all* the
DHT in a man's body, and all the other androgen still up there in his scalp
skin.
Fuzz
> >What about spironolactone? Well, we can look at other studies that
> >tested spiro in a very similar fashion: "Antiandrogenic Effects of
> >Topically Applied Spironolactone on the Hamster Flank Organ",
> >Arthur Weissmann et al, Archives of Dermatology, Vol. 121, Jan 1985.
> >
>
>
> Topical spironolcactone works well on Hamsters and rodents, but it's
activity
> in human skin applied topically is weak and equivocal.
Maneless believes that topical spironolactone is weak and equivocal. Is
this compared to RU58841 or without any comparison to other treatments?
Without making a comparison, how strong/weak is topical spironolactone as a
receptor blocker? I have read some past posts on its antagonistic activity,
but could someone summarize in hair loss terms? Meaning...if you apply
topical spironolactone, what % of DHT and T is roughly blocked?
> THEY COULD HAVE JSUT RAISED THE DOSE OF THE RU58841 AND GOTTEN BETTER
RESULTS
> FOOL
This brings up another question. They could have also raised the
spironolactone dosage too. What is the upper limits of topical
spironolactone (before a flat response is reached)? Is 5% basically the
highest concentration for the most beneficial results?
--Fuzz
Manelessrjd
>>can be achieved with the careful
>>use of other drugs like spironolactone.
Spironolactone is weak and equvocal applied topically in humans no matter how
much you use it's not gonna be our answer.
BTW Dr. P. sells spironolactone, and I'll just bet you would say his is
"careully used* huh?
Manelessrjd
>have a pretty reasonable way of making fairly direct comparisons
Is it gonna be human men or the stumptail macaques?
I ask because Bryan says I can't use the hamster or other animals, or even
human women.
I can only use man and stumptail macaques. That's it. Bryan protests big time
when I try to use anything else.
I'm sure Bryan wil only use men or Stumptail macaques as that's all he'll let
me use.
Well, let's see.............
>They used the standard hamster flank organ test to see the biological
>effect of this drug.
Bryan, Bryan, Bryan you said I could not use this type of model. What are you
doing Bryan? Are you scamming?
1. They could've raised the odose of the RU58841 in this study and increased
the flank organ more, duh.
2. Bryan, let's go look at all the furry little rodent studies inasmuch as you
opened the door to it. Now I can prove that oral antiandrogens
have a more powerful effect than finasteride.
Thereby proving that we don't need this *stuff* from Dr.P., we merely need
better antiandrogens. Alright.
Are we in agreement?
I get to use the furry little creature studies to prove that oral
antiandrogens are more effective than finasteride at growing hair. I get to
use flank organs, or whatever other parts of their bodies are regulated by the
androgens, right? After all, you just did, so why can't I?
Hey everybody I can now prove that the oral antiandrogens are more effective
than finasteride establishing that all we need is more androgen suppression and
we are out of our mess.
> They applied varying doses of RU58841 in ethanol
>to only one flank organ of one group of hamsters, and ethanol only as
>a control to another group. A third group was castrated and had ethano
Before closing this post I wanted to remind you of something: THEY COULD HAVE
JUST INCREASED THE DOSE OF THE RU58841 AND GOTTEN A BETTER EFFECT ON THE
HAMSTER FLANK ORGAN.
One more thing Bryan, do you have a full head of hair?
Manelessrjd
It's not the potency of spironolactone. It has good potency. It's just not
very active in skin applied topically.
>Is
>this compared to RU58841 or without any comparison to other treatments
All by itself Fuzz. Without any comparrisson to other treatments However, it
does have some affect applied topically in some people. You might be one of
them. It is definately worth a try. Formulate in the way it's most succesful,
and pray.
>Without making a comparison, how strong/weak is topical spironolactone as a
>receptor blocker
It's receptor blocking ability is actually OK.
It's problem lies elsewhere. Our only chance with this drug is to formulate it
in the best way possible and hope were one of the lucky one's. We want to get
a good dose of the spironolactone.
We should also be on oral finasteride too.
Topical minoxidil too.
> Meaning...if you apply
>topical spironolactone, what % of DHT and T is roughly blocked
I don't think there's ever been testing of this in humans, and you cana't
really compare hamsters and stuff like that when you apply it topically because
it's so much easier to get the spironolactone into these rodents topically.
Their skin is a lot thinner, and it passes from the top of their skin into
lower levels of their skin much easier.
Spironolactone is metabolized into a weak antiandrogen very fastly. This might
be part of the problem as well.
>This brings up another question. They could have also raised the
>spironolactone dosage too.
You might have something here Fuzz. I honestly don't know. If you look at the
past posts of mine where I talk about using topical spironolactone I talk about
going to 10%.
I'm not going any higher, but I'm definately gonna do 10%, and I'm gonna pray.
Keep in mind that since spironoalctone is very rapidly changed into a weak
antiandrogen by way of metabolization it may not matter how much we use. If it
changes into a weak antiandrogen fast enough it could theoretically take more
than we could possibly use. And then there's the issue of how much easier it
is to absorb stuff into rodent skin than human skin.
> What is the upper limits of topical
>spironolactone (before a flat response is reached)
This is what I'm concerned about with spironolactone. The flat response
point.
due to it's rapid metabolization or because of absorption problems, or some
other problem or multiple problems, it may not work in lots of people no matter
how much they use.
Of course, once again, it does give some benefit to some people, and you might
be one of them.
>Is 5% basically the
>highest concentration for the most beneficial results
I'm gonna go at least 10%. I'm gonna start a new plan in about 3 or 4 weeks.
I'm not taking anything right now.
What I'm gonna do is probably close to what you're doing if not exactly the
same thing.
I'm waiting for medication to come in the mail.
Fuzz, In a month I'm gonna have some news on that new minoxidil like drug from
Bristol Meyers that's 1000 times as strong as minoxidil.
I think it's gonna be better than minoxidilat growing hair. I'll let you know
in a month by a post in the ng. It's starting phase 2 human studies this
August.
If it comes to market it will be in about 3 years.
ugh.