check this out, its a sweet moma
by the looks of this, spironolactone the SH$T
i got this out of the old archives, this bryan guy wrote it, he was a very knowledgable dude; even for 3 years ago
pretty much the article medical stuff goes on to say that spironolactone blocks DHT by 67%
chaaachig
The oldtimers here will recall that for years Dr. P has occasionally
referred to a certain unspecified medical study that found that
spironolactone has a VERY high affinity for the androgen receptor;
indeed, that it binds to the androgen receptor with fully 2/3 of the
affinity that DHT itself has!
I recently stumbled across the study while looking for something
else. This would be: "The Use of Human Skin Fibroblasts
to Obtain Potency Estimates of Drug Binding to Androgen
Receptors", Eil and Edelson, J Clin Endocrinol Metab 59:51, 1984.
They found that spironolactone had BY FAR the strongest binding
affinity for the human androgen receptor of all the antiandrogens
they tested, and this included cyproterone acetate and flutamide
(NOT hydroxyflutamide). I'm going to reproduce the entire list
of substances that they tested, and the Relative Binding Affinity
that they measured for each one, expressed as a percentage of DHT
itself. A couple of brief notes, first: at the top of the list are R1881,
DHT, and testosterone, all with relative binding affinities set at 100%.
R1881 is a powerful synthetic androgen that's frequently used in
studies like this because it's not metabolized into anything else.
It "stays put", in other words! And you'll probably wonder why
testosterone is also listed at 100% along with DHT. This is the
actual result they measured, and apparently is because after they
added the testosterone to the cell culture, most of it was
metabolized into DHT by 5alpha-reductase.
Here's the complete list of substances they tested, and their RBAs.
They are listed in descending order of activity. Afterwards I'll have
a couple of interesting quotes from the study:
R1881 (methyltrienolone, a powerful synthetic androgen)
100.0
DHT
100.0
Testosterone
100.0
Spironolactone (our good friend spironolactone!)
67.0
Danazol (an androgen agonist)
41.4
R2956 (a synthetic antiandrogen from Roussel-UCLAF)
14.8
Megesterol acetate
13.6
Cyproterone acetate
12.5
Medroxyprogesterone acetate
11.6
Progesterone
6.6
Estradiol
4.9
Androstenedione
2.0
Canrenone
0.84
4-Hydroxyandrostenedione
0.79
17-Hydroxyprogesterone (note: this is NOT 11alpha-hydroxyprogesterone)
0.42
Flutamide
0.079
MSD L-642,317 (this is in the finasteride family of compounds)
0.038
Testolactone
0.0029
Cimetidine
0.00084
MSD L-642,022 (another in the finasteride family)
<0.0005
Diphenylhydantoin
<0.0005
Diazoxide (this is a drug similar to minoxidil)
<0.0005
That's the complete list. Now here are some comments from the
"Discussion" section: "The advantages of using dispersed cultured
fibroblasts for the comparison are 2-fold: 1) the receptors are from
human cells, and 2) the cells are intact, and therefore, the assay
system simulates *in vitro* many of the characteristics of the *in vivo*
interactions of the compounds with androgen target tissues, such as
nuclear localization. The disadvantages include the fact that these
*in vitro* receptor studies do not define whether an inhibitor of binding
is an agonist or antagonist *in vivo*. Also, metabolism of the
compounds to more or less potent congeners, which may occur after
clinical use of these drugs, may not be reproduced in the dispersed
cell fibroblast assay system. This may account for the unexpected
high potency of spironolactone, which is cleared rapidly *in vivo*,
and the unexpected low potency of flutamide, which may require
hydroxylation for full antiandrogenic activity..."
"...The results of this study indicate that spironolactone is an
extremely effective competitor for the androgen receptor, even
more potent than previously reported by others. This probably
accounts for its therapeutic efficacy in hirsute women and for the
high frequency of impotence and gynecomastia in men given the
drug. If it can be administered in a form that minimizes its
metabolism to canrenone, a much weaker androgen receptor
binder, then its antiandrogenicity *in vivo* may be even further
enhanced. This could be of potentially great benefit to patients with
hirsutism, acne, prostatic hypertrophy and/or carcinoma, and other
disorders thought to be due to excess androgen action."
Bryan
