Could this be the real cause of PFS

General Discussion
#37

I promise you I’ll come back to this thread and post the publications I found on finasteride being a non-competitive inhibitor you have my word on that @arkaeik where did you get your info that finasteride was a non-competitor if you can please post as I don’t have a copy and paste option on this xbox. Honestly I wouldn’t trust any info that comes from the FDA as they are just fed what Merck tells them.

What if it did bind to the receptor sites irreversibly disabling them? I couldn’t find info that the body regenerates new receptors. There really isn’t information out there about the receptors and finasteride- this is just my hypothesis about the receptor sites not absolute fact but that’s why I’m reaching out to guys for help and to find answers.

#39

3 posts were merged into an existing topic: Discussion about estrogenic symptoms

#40

I get that u think this, but i don’t think this is the case. As I said, I took SSRI and have the exact same persisting symptoms, without SSRI being an irreversible ihibitor. I think gene alterations is a way more plausible explanation for the persistance of symptoms.

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#41

Every drug has different mechanisms although the sides are correlated. The Italian study had suggestered there was an abnormality at the AR level so this would go hand in hand with what I was saying about finasteride bonding to the receptor sites mutating them. This would also explain why people are having success with tribulus and l-carnetine which both resensitive the androgen receptors so that we can actually feel testosterone and DHT working. The solution to this madness might be finding a way to activate the androgen receptors or create new ones

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#42

@Blueryan123 , the following should abolish any of your doubts about the recycling of AR:

D. K. Lee and C. Chang, “Expression and Degradation of Androgen Receptor: Mechanism and Clinical Implication,” J Clin Endocrinol Metab , vol. 88, no. 9, pp. 4043–4054, Sep. 2003.

The life cycle of AR is followed in the above article, from transcription of AR mRNA, to degradation by proteosomes. Degradation of misfolded/denatured proteins is also touched-upon. There are also estimated half-lives of AR provided that are hours, not days, months, or years.

Chawnshang Chang is one of the world’s leading androgen receptor researchers. He might even be considered the father of AR research, since he was the first to isolate and clone human AR. So, this is coming from a true authority on the matter.

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#43

Why was @blueryan123 banned?? Really worried about the guy we should at least give him another chance on the forum.

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#44

Your theory, thought logic and mindset is ahead of the curve. Anyone that has an issue with any of the thoughts you are proposing here is foolish.

I break down your thoughts as following:

Is Finasteride effecting the enzyme? And if so in a reversible or irreversible way?

Is finasteride effecting the receptors? And if so in a reversible or irreversible way?

Also another thing that should be seriously considered is despite the majority of information available indicating finasteride being a competitive inhibitor, is there another way it acts in a inreversible way?

These questions should be discussed in much greater detail. For now what I can add is that I have taken a drug called Mifepristone several times since 2017. It’s the female abortion drug which blocks progesterone receptors starving the fetus.

Mifepristone also blocks cortisol receptors and other receptors. It almost cured me in 2017 after a three day 50mg cycle of it. It cured me in the “snap back”. Meaning in the weeks following coming off of it. Mifepristone acts as an Antagonist binding to receptors as you stated “blocking them”. What’s going to happen when you block your receptors is that they are going to up regulate their sensitivity level in an attempt to make “their hormone” still be able to react with them them despite being blocked. Now if your receptors are down regulated this could be a possible fix because you would be up regulating down regulated receptors

I’m on day three of a 200 mg cycle of mifepristone currently. I will report my results in the up coming weeks

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#45

Finasteride shares significant structural similarity with testosterone and DHT. It is thus possible that finasteride may act as a ligand to the androgen receptor (AR) in addition to its role as a 5α-reductase inhibitor. … Peroxiredoxin-1 (Prx1) is a novel endogenous modulator of AR binding to DHT.

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#46

Interesting…

I’m not sure why he was proposing that Fin permanently blocks AR’s? By what mechanism? I guess in order to really know if what you posted abolishes any doubts about how he is saying fin permanently blocks AR’s we would need to know what his proposed mechanism is of how Fin is doing this ? Either way we have seen no evidence that Fin does this.

Initially though he was talking about the enzyme and if Fin works as a reversible or nonreversible inhibitor of the enzyme. And I think he has a point about this. I do remember reading Fin is a Nonreversible inhibitor years back. Now (like he was saying) those sources are just gone or at least harder to find…

Instead now everything says Fin is a competitive inhibitor which suggests it’s reversible. So I find this suspicious as well. Also if Fin is a competitor inhibitor it may still be acting in a nonreversible way. I think what it’s doing to the substrate should be looked at in more detail. Here:

http://cbm.msoe.edu/crest/posters/2015CUWSP/15finasteride.html](http://cbm.msoe.edu/crest/posters/2015CUWSP/15finasteride.html)

“Mechanism-based inactivation of 5α-reductase type 2 by finasteride showing a hydride reaction occurring between finasteride and NADPH that results in a covalent bond between finasteride and the cofactor. [R = -C(=O)-NH2; PADPR = 2’-phosphoadenosine-5’’-diphosphoribose; A-H = TYR58.7]”

We should look into this in more detail? What does this mean exactly? Covalent bond is permanent correct?

Also this:

“Although it is accepted as an alternate substrate and is ultimately reduced to dihydrofinasteride, this proceeds through an enzyme-bound NADP−dihydrofinasteride adduct”

“the binding of NADPHto the enzyme followed by the substrate”

Maybe you guys should try to get tested to see if you have still have dihydrofinasteride in your blood. I did not take fin so this is not an avenue for me to take.

#47

Any updates on mifepristone?

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