Cortene drug trial/Astressin B

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Maxin
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Cortene drug trial/Astressin B

Unread post by Maxin »

Ok everyone bear with me while I try to explain this. I feel like this could be a big part of the puzzle for pssd and pfs peeps. As I’ve said, taking an ssri caused disabling fatigue that I’ve dealt with now for 12 years. And in the neurotoxicity group on Facebook, there are many of us that have disabling fatigue now. But as you read, you will se how this new drug also connects to sexual dysfunction and serotonin receptors.

So as I’m part of pssd communities, I also follow a lot in the cfs world. I’ve always felt cfs had connections to serotonin dysfunction as I’m a perfect example. I sometimes wonder how many cfs people do not connect the dots on what meds they were on when their cfs started.
I also believe that my problems stem from issues in the hpa axis. This is because any success I’ve had has been when I manipulate this axis. Whether it has been steroids, thyroid, or ru 486. But there some feel back loop and I always crash.


So a company is now trialing a new drug called Cortene. Their hypothesis is that a maladaptation within the limbic system, which shapes our response to stress, may underlie ME/CFS.  Specifically that a receptor called CRF2, which triggers neurons to release serotonin, has become unusually prevalent in parts of ME/CFS patients’ brains. Cortene believes that the elevated release of serotonin – in response to even small levels of stress – in turn causes ME/CFS. And this elevated serotonin level is due to 5ht1a receptor desensitization. I don’t believe it’s a coincidence that many people after SSRI exposure are diagnosed with this generally rare illness called cfs.


Here are some comments from people that I copied as I found-


“In terms of how the HPA-axis reset is actioned, the difference between CT38 and mifepristone is where they inhibit the HPA-axis. Here is the HPA-axis (and how it activates as part of the fight-or-flight response):

Stress ➤ Hypothalamus releases CRH ➤ Pituitary releases ACTH ➤ Adrenal glands release cortisol ➤ Activates glucocorticoid receptors

CT38 inhibits the effect of CRH (corticotropin-releasing hormone) by blocking the corticotropin-releasing hormone receptor 2 in the pituitary, and this then inhibits the whole HPA-axis.

Whereas mifepristone acts further downstream in the HPA-axis, by blocking the glucocorticoid receptor 2 (a cortisol receptor), preventing cortisol from activating the glucocorticoid receptor.

So this is how both drugs achieve an axis reset in their own ways; presumably CT38 must offer some additional advantages by inhibiting the HPA-axis further up, otherwise why would Cortene be trialing CT38 for ME/CFS.”

“Or maybe with CT38 they are not aiming to reset the HPA-axis, but rather reset some more local feedback loop just within the limbic system.”

“It would it be correct to say that another one of the big differences between SSRI's and CT38 is that SSRI's seek to ameliorate depression by moderately increasing serotonin via blocking its reuptake, whereas CT 38 - being an CRF2 agonist - seeks to spike serotinin much higher in an effort to trip the desensitized 5HT1A auto-receptors, which are responsible for causing the CRF2 receptors to internalize, thereby turning off ME/CFS. This would explain why lower doses of CT38 cause 'ME/CFS-like' symptoms, but higher doses would theoretically turn them off.”

And in an article about how Cortene was created-

“Sometime before, he’d come across an intriguing drug (CT38) being developed by the pharmaceutical division of Proctor & Gamble. CT38 prevented muscle wasting in animals, and it had been through a Phase 1 clinical trial and tested safe in healthy humans. Despite the promising test results, after Proctor & Gamble decided to exit the drug industry entirely, CT38 was left available for licensing. [...] Pereira was at a cocktail party discussing his drug with a well-known Stanford doctor, who was talking about some immune findings in a strange disease called ME/CFS. Pereira had not heard of the disease before, but the immune findings, and ME/CFS in general, seemed eerily reminiscent of the data he’d seen produced for CT38."

http://www.onlinejacc.org/content/49/4/461

Now, because this drug won’t be approved for some time, there is another that is nearly identical called Astressin-B. Please note that this drug improves sexual function in rats.

“Astressin-B is a nonselective corticotropin releasing hormone antagonist that reduces the synthesis of ACTH and cortisol. Reducing ACTH synthesis, it improves the sexual drive of rats under stressing conditions.”



So you can buy hairloss products that supposedly contain this peptide, astressin-b, which is a crf2 antagonist.
It looks like from that astressin-B is a non-selective CRF1 and CRF2 antagonist, and astressin2-B is a selective CRF2 antagonist. Since we would want to target CRF2, astressin2-B would be best, but the astressin-B found in hair loss products might suffice. The problem is getting it to absorb and across blood brain barrier.


Some links:


https://www.healthrising.org/blog/2018/ ... ypothesis/

http://www.onlinejacc.org/content/49/4/461
Maxin
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Re: Cortene drug trial/Astressin B

Unread post by Maxin »

And note that the drug was first discovered to prevent muscle wasting in animals. This is something seen a lot in pfs.
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TalkingAnt
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Re: Cortene drug trial/Astressin B

Unread post by TalkingAnt »

Peptides are probably too big to be absorbed dermally. It is common to see scam products suggest otherwise. So peptides are typically injected or taken orally if they are stable in stomach acid.

Phosphatidylserine may have similar effects (see discussion section):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503954/
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Maxin
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Re: Cortene drug trial/Astressin B

Unread post by Maxin »

Yeah I’m not suggesting astressin b as the topical would not absorb properly. I’m just excited to see what happens with Cortene. I think it will have uses that go beyond cfs treatment. It is given by infusion.
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Twentyoneguns
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Re: Cortene drug trial/Astressin B

Unread post by Twentyoneguns »

I feel SSRIs were responsible for my CFS experience. In 2010 while I was away on a long trip I simply ran out of Fluoxetine so effectively went cold turkey....I didnt seem to suffer any consequences immediately and certainly didn't associate the onset of CFS a few months later with the sudden withdrawal of Fluoxetine.

The severity of the fatigue was terrible, I could barely walk. This state continued for about 3 months when I had a sudden positive step change in the fatigue level...not back to normal but I certainly enjoyed my partial return to health. Three months later after a very tiring day I went to lie down for an hour...when I woke I was completely back to my pre CFS state....not just a bit better and a gradual improvement over weeks...instantly ...a miracle!

This happy state remained for 11 months. I certainly made the most of my health during this period. I then caught a bad cold and and the CFS returned in force, this time it continued for what seemed an interminable 5 years.

At this point I was diagnosed with cancer and had to undergo chemotherapy and radiotherapy...the side effects of this were terrible in conjunction with the CFS. The recovery from the treatment followed the predicted time scale....miraculously my CFS disappeared as I recovered.

Unfortunately my depression returned and I fought the desire to start the Fluoxetine again....however things got so bad I did return, but it did not seem to help, it was at this point that my doctor suggested switching to Sertraline....what a fucking disaster....instant PSSD....2 years later Im still in the same state.

I do wonder if the cancer was due to the effects of the SSRIs too.

I still hold onto the idea that like the CFS, the PSSD will suddenly go into remission.

Just my story....slowly joining the dots.
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Maxin
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Re: Cortene drug trial/Astressin B

Unread post by Maxin »

I wonder if the chemo somehow helped your cfs? And yes I’m sure the cancer was related to the ssri. My entire biochemistry seems changed after ssri. I’m glad you healed from the cancer.

This is why I believe in terms of my cfs it’s not some underlying virus but a switch that got flipped. Because I’ve been able to flip the switch very termination a few times. And why Cortene seems intriguing for many reasons. I’m trying to find a way to get a hold of this peptide to trial on myself. I can order it through research labs. Running in to problems with daltons and absorption. And this kind of things is not my strong suit!
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Meso
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Re: Cortene drug trial/Astressin B

Unread post by Meso »

Cyproheptadine, which I started trialing yesterday, drastically reduces ACTH release and is used off-label for Cushing's. It does so by interfering with CRF function on the pituitary, possibly by blocking CRF receptors.

Cypro also happens to be a potent anti-serotonergic agent used in management of serotonin syndrome. It's an antagonist/inverse agonist at: 5HT1A, 2A, 2C, 3, 6, and 7.

Downside is it's also a potent antihistamine, and blocks dopaminergic and muscarinic receptors at higher doses, but that shouldn't be a problem if you are on dopaminergic + cholinergic agents (I'm on Donepezil + Rasagiline, but I wonder if the natural ligand is enough to displace Cypro from the receptors, otherwise 'd need different agents acting as direct agonists with higher receptor affinity than Cypro).

Anyway, this is going to be interesting.
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Jaxx
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Re: Cortene drug trial/Astressin B

Unread post by Jaxx »

Mesolimbo wrote:Cyproheptadine, which I started trialing yesterday, drastically reduces ACTH release and is used off-label for Cushing's. It does so by interfering with CRF function on the pituitary, possibly by blocking CRF receptors.

Cypro also happens to be a potent anti-serotonergic agent used in management of serotonin syndrome. It's an antagonist/inverse agonist at: 5HT1A, 2A, 2C, 3, 6, and 7.

Downside is it's also a potent antihistamine, and blocks dopaminergic and muscarinic receptors at higher doses, but that shouldn't be a problem if you are on dopaminergic + cholinergic agents (I'm on Donepezil + Rasagiline, but I wonder if the natural ligand is enough to displace Cypro from the receptors, otherwise 'd need different agents acting as direct agonists with higher receptor affinity than Cypro).

Anyway, this is going to be interesting.
Curious to see what happens! I was planning to combine pramipexole with cypro, but as most people here had really bad reviews on cypro’s side effects i combined it with kudzu instead.
Maxin
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Re: Cortene drug trial/Astressin B

Unread post by Maxin »

Mesolimbo wrote:Cyproheptadine, which I started trialing yesterday, drastically reduces ACTH release and is used off-label for Cushing's. It does so by interfering with CRF function on the pituitary, possibly by blocking CRF receptors.

Cypro also happens to be a potent anti-serotonergic agent used in management of serotonin syndrome. It's an antagonist/inverse agonist at: 5HT1A, 2A, 2C, 3, 6, and 7.

Downside is it's also a potent antihistamine, and blocks dopaminergic and muscarinic receptors at higher doses, but that shouldn't be a problem if you are on dopaminergic + cholinergic agents (I'm on Donepezil + Rasagiline, but I wonder if the natural ligand is enough to displace Cypro from the receptors, otherwise 'd need different agents acting as direct agonists with higher receptor affinity than Cypro).

Anyway, this is going to be interesting.
Keep us posted on your experience. Cypro is one I still haven’t tried, surprisingly. And I’ve tried a lot!
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Re: Cortene drug trial/Astressin B

Unread post by Ghost »

This thread is interesting. I'm excited to see how this turns out.
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