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How does Metyrapone work?

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I'm gonna send this over to neuroscience&pharmacology, those guys will be better suited to helping you.
 
You don't want to fuck about with your ACTH levels, CRF levels or corticosteroid levels either unless you medically speaking, haven't got a choice. Adrenal insufficiency is no laughing matter. I know two people who either don't produce ACTH or produce very low levels of it.

One of the two has Rett syndrome and MERRF, and she got fucked over by her boss at her old works, and being that she is in the US, and how the USA has a completely fucked-up, arse over tit sheep buggering backwards healthcare system thats not worth a damn. The cunt fucked her over with her insurance, and she had difficulty getting her meds for a while because of it, and she could easily have died from the adrenal insufficiency, especially when things like her seizures are taken into account with the stress they put on people. The other lass, my stalker and ex gf, she didn't have such a severe degree of ACTH-deficiency related adrenal insufficiency, but it still made her very tired, absolutely exhausted most of the time. Low blood pressure, difficulty reacting to stressful occasions in life.

Seriously, fucking with your ACTH levels or messing with your glucocorticoid system, or CRF/CRF-BP is not something you want to do. Our bodies put a lot of effort into having feedback mechanisms and maintaining a carefully balanced condition of homeostasis where the hypothalamic-pituitary-adrenal axis is concerned and you really, really don't want to disrupt it. Nothing good will come of it, either too much or too little activity of these complicated interlinked systems will cause major trouble, and severe adrenal insufficiency or severe excessive glucocorticoid/mineralocorticoid levels can both be fatal.

Trust me on this one, I've seen what adrenal insufficiency, and specifically through insufficient productivity of ACTH looks like, and whilst I admit, both the ex gf/stalker and the chick with Rett's syndrome who had the far more severe adrenal insufficiency, both of them ARE stunningly fucking well hot=D, you don't want to BE in their position, when it comes to corticosteroid issues.
 
say medically speaking I dont have a choice, would this drug help someone with too much CRF1 activation?
 
Jesus christ man, stop making up disorders or attributing whatever psychiatric ailments you have to mechanisms which have never been strongly linked to your problems just because some genetic test shows that the genes that are somehow/what related to said systems aren't found in a majority of the population when we(as in the human race) has almost no understanding of said genes and little understanding of the systems you are attributing said symptoms to. You are going to end up making your problems worse, create new ones, or seriously fuck yourself up. Go to a doctor, tell them what problems you are having, and listen to their advice.

You should just throw the results of said test away, outside of how you metabolize drugs the test is a novelty, for fun, it is interesting but pretty much fucking useless for diagnosing/treating psychiatric illness. Especially something like "anxiety".
 
damn dude have u been keeping that frustratiion inside of u? how are u so bothered by an online guy asking question? get off my nuts and mind ur buisness, ruining my thread already. U and that other guy. But I think U just wanted my attention , here u go becuase U dont get any in real life.
 
I don't want your attention, I want you to go away. You are practically spamming the forum with ridiculous threads and asinine questions when you don't have the experience/knowledge to understand the complex answers to the questions you are asking and even if you could it would bring you nowhere closer to solving your problems. From what you have posted I have gathered that you have anxiety, took a genetic test, and now are going through the list, looking at every single gene you have which is found in a minority of the population, cliff noting the function of said genes, and then grasping at straws trying to link said genes to your illness.

You aren't just wasting your own time, you are wasting everyone else's and wasting bluelights resources.
 
You'd already be under the care of an endocrinologist if you had severe issues with CRF, with ACTH, with CRF-BP, or any other gluco/mineralocorticoid. And Coolwhip is right, you need to see a doctor, not try to selfdiagnose through us, based on the results of a publicly available genetic profiling site, which isn't fit for such purposes.

And without meaning insult, coolwhip is quite correct in that you obviously don't have the medical knowledge to interpret tests that did have value if you did get such a thing. And that you could very easily do yourself harm that is both lasting, serious, and potentially permanent. Or even kill you. Like for example that fiasco that saw you ordering NMDA. That could have turned you into a fucking vegetable, after first causing seizures, at least if the seizures didn't kill you. It would have reduced you to something like an alzheimer's patient in the end stages if you'd fucked about with it.
 
No, this will not help you, and in fact could seriously mess you up. Don't play with your steroid levels or the hypothalamic-pituitary-testicular axis. (HPTA)

From what you have posted I have gathered that you have anxiety, took a genetic test, and now are going through the list, looking at every single gene you have which is found in a minority of the population, cliff noting the function of said genes, and then grasping at straws trying to link said genes to your illness.

You aren't just wasting your own time, you are wasting everyone else's and wasting bluelights resources.
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This.

Please go see a doctor or psychotherapist and treat your depression/anxiety from first principles rather than "blaming" it on a random gene and hoping a miracle chemical will "balance it all out again".
 
sekio said:
No, this will not help you, and in fact could seriously mess you up. Don't play with your steroid levels or the hypothalamic-pituitary-testicular axis. (HPTA)



This.

Please go see a doctor or psychotherapist and treat your depression/anxiety from first principles rather than "blaming" it on a random gene and hoping a miracle chemical will "balance it all out again".
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can u explain why this drug wouldnt work for an overactive CRF1? and dont worry this is my last thread to the other guy.
 
"Overactive CRF1" is a poorly defined symptom, do you mean your body produces too much CRH, too many CRF1 receptors, the receptors are malformed and are overactive with no ligand binding, there are not enough receptors and CRF1 is overproduced, etc? And how do you know? Again, going on the basis of a SNP is not considered enough evidence clinically, you should have blood work done...

In any case taking a drug that blocks cortisol synthesis will not have a direct impact on CRH and certainly won't have an immediate effect on CRF1 receptor up/downregulation. Under no circumstances can a small-molecule drug directly "fix" genes though.

There are currently no approved drugs or herbs that directly block/bind to CRF1 receptors, so you're kind of on your own.
 
sekio said:
"Overactive CRF1" is a poorly defined symptom, do you mean your body produces too much CRH, too many CRF1 receptors, the receptors are malformed and are overactive with no ligand binding, there are not enough receptors and CRF1 is overproduced, etc? And how do you know? Again, going on the basis of a SNP is not considered enough evidence clinically, you should have blood work done...

In any case taking a drug that blocks cortisol synthesis will not have a direct impact on CRH and certainly won't have an immediate effect on CRF1 receptor up/downregulation. Under no circumstances can a small-molecule drug directly "fix" genes though.

There are currently no approved drugs or herbs that directly block/bind to CRF1 receptors, so you're kind of on your own.
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again explain why it wouldnt work? if it stops cortisol synthesis its bound to downregulate CRF1 too.
Look it says I have 3 different mutations in my CRF1 gene:
https://www.selfdecode.com/gene/crhr1-it1/
https://www.selfdecode.com/gene/mgc57346-crhr1/
https://www.selfdecode.com/gene/crhr1/


Well you cant see it but they are marked as red flagged for me, And overactivation of CRF1 is more anxiety, thats why I connect CRF1 to my social anxiety.
But there are no description on the first 2 genes, But im taking it as they are bad mutations and increase CRF1 expression. I dont know whats wrong with my CRF1 but I think its too much activity causing problems with ACTH. I think other then that my cortisol is normal I dont think I have any tumours or cushings syndrome or whatever its called. But I really think theres a problem with my CRF1.
CRF2 and CRH is fine I think. Thats why I respond so positive to cortisol decreasing herbs EG (rhodiola rosea +Ashwagandha + Phosphatidylserine + Holy Basil )

There are currently no approved drugs or herbs that directly block/bind to CRF1 receptors, so you're kind of on your own.
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Antalarmin is a drug that blocks CRF1 but I dont know if thats approved or whatever.
 
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if it stops cortisol synthesis its bound to downregulate CRF1 too.
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How do you know that? CRF1 activity is independent of cortisol levels, CRF1 does not bind cortisol at all. The brain is not set up like a Rube Goldberg machine where every single neurotransmitter effects everything else...

Antalarmin is not approved by the FDA or any other medicolegal body. Fun fact, a related CRF1 antagonist, pexacerfont, showed no benefits over placebo for treatment of anxiety.

But I really think theres a problem with my CRF1.
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A week ago you had a problem with CB1, before that it was NMDA receptors. Treatments were suggested and the topic was discussed both times but all the while you seem to bury your head in the sand and happily ignore any sort of educated advice in the frantic search for a miracle cure. Maybe tomorrow you will come out with another protein you are certain you can blame for all your worries because you have "too much" or "too little".

You are also ignoring the fact that websites like selfdecode are not meant to substitute for a doctor or geneticist and should not be used to plan treatments.

selfdecode faq said:
You should never take any drastic action or an action that has significant side effects based on your genetics. Currently, the best way to use your genes is to motivate you to take a healthy action that you should already be taking.

If you see something that may alarm you, make sure to speak with your doctor to understand what these results mean.

The FDA says that it has the ability to regulate genomic interpretation (whether we like it or not) because people sometimes take drastic action based on genetic results.

You shouldn't make any changes in medical behavior based on your genes without discussing with your doctor.
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I still think you are missing the forest for the trees and need to treat your condition in a more rational, holistic fashion. But then again, useful advice seems to be completely ignored when it comes to this topic, for all I know you'll simply move down the list and start blaming your problems on the next SNP you can find.
 
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Why not start by seeing a doctor? and smoking some green, hash etc.? at least you know that you aren't going to keel over and die
from smoking some weed. A lot of people do find it helpful for anxiety.
 
sekio said:
How do you know that? CRF1 activity is independent of cortisol levels, CRF1 does not bind cortisol at all. The brain is not set up like a Rube Goldberg machine where every single neurotransmitter effects everything else...

Antalarmin is not approved by the FDA or any other medicolegal body. Fun fact, a related CRF1 antagonist, pexacerfont, showed no benefits over placebo for treatment of anxiety.



A week ago you had a problem with CB1, before that it was NMDA receptors. Treatments were suggested and the topic was discussed both times but all the while you seem to bury your head in the sand and happily ignore any sort of educated advice in the frantic search for a miracle cure. Maybe tomorrow you will come out with another protein you are certain you can blame for all your worries because you have "too much" or "too little".

You are also ignoring the fact that websites like selfdecode are not meant to substitute for a doctor or geneticist and should not be used to plan treatments.



I still think you are missing the forest for the trees and need to treat your condition in a more rational, holistic fashion. But then again, useful advice seems to be completely ignored when it comes to this topic, for all I know you'll simply move down the list and start blaming your problems on the next SNP you can find.
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No cortisol is it . I wont change my mind dont worry and like I said this is my last thread so I just wanna ask a few last questions.
You still havent answered why Metyrapone wouldnt work.
 
Let me flip this on you, explain to me why you think metyrapone would work. If anything, decreased cortisol synthesis caused by metyrapone would result in increased production of CRF and thereby increased agonism/stimulation of CRF1, the opposite of your desired effect.
 
sekio said:
Let me flip this on you, explain to me why you think metyrapone would work. If anything, decreased cortisol synthesis caused by metyrapone would result in increased production of CRF and thereby increased agonism/stimulation of CRF1, the opposite of your desired effect.
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but doesent it decrease ACTH which is what CRF1 activates for stress?

what about Flucanazole,Spironolactone or Mifepristone would they work to block cortisol?
 
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ACTH secretion is what induces CRF release, not the other way round. And it comes from a propeptide called POMC, proopiomelanocortin, which is selectively cleaved into ACTH, enkephalin (forget which one), the melanocyte-stimulating hormone, its one pre-peptide chain that gets cleaved as appropriate into a bunch of neurotransmitters. FORGET fucking with your cortisol, CRF, CRF-BP or ACTH levels, ACTH receptor activation etc.

As for your second question-is that actually an honest question, or are you just taking the piss and trolling?
 
Limpet_Chicken said:
ACTH secretion is what induces CRF release, not the other way round. And it comes from a propeptide called POMC, proopiomelanocortin, which is selectively cleaved into ACTH, enkephalin (forget which one), the melanocyte-stimulating hormone, its one pre-peptide chain that gets cleaved as appropriate into a bunch of neurotransmitters. FORGET fucking with your cortisol, CRF, CRF-BP or ACTH levels, ACTH receptor activation etc.

As for your second question-is that actually an honest question, or are you just taking the piss and trolling?
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No im not F#cking trolling. Why would I be?

Isnt it this way ? CRH-> CRF1> ACTH->Cortisol

I know Mifepristone is used for abortions but if it blocks cortisol or can help me im willing to try anything.

But if you had an Overactive CRF1 (which I think I have) would that induce more ACTH release then go in a cricle and just go higher and higher , does that make sense? So if my CRF1 keeps activating (due to mutations in the gene) and stress keeps buildin up then ACTH activates and that Activates CRH release and CRH further activates CRF1 and then CRF1 again activates ACTH and then it just goes in a circle and goes higher and higher, does that make sense?


is this pic correct?
Post-The-Endocrine-Journey-1.jpg
 
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So what I want is a Glucocorticoid receptor antagonist right? Maybe Mifepristone ,Flucanazole , Miconazole and Ketoconazole are bad choices but they block this, But what about Spironolactone ? its an Glucocorticoid receptor antagonist also.

So out of this list which would be the best to block cortisol?
Metyrapone
Mifepristone
Flucanazole
Miconazole
Ketoconazole
Spironolactone
(Anything else??)

Im going by this pic: so if my thinking is correct (which it rareley is) a glucocorticoid antagonist would decrease all types of cortisol? In the purple and green places of the pic?
1024px-Steroidogenesis.svg.png
 
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