FOUND THE CAUSE OF PSSD!!! SEROTONIN - PPARy - nNOS *REVEALED*

This is a place to post research you have done on the topic along with your conclusions.
Oleya
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Re: FOUND THE CAUSE OF PSSD!!! SEROTONIN - PPARy - nNOS *REVEALED*

Unread post by Oleya »

PsychoGenesis wrote: Thu Oct 03, 2019 12:02 pm must be easy to test with a PPARy agonist like pioglitazone

PPARa agonist fenofibrate seems to have the opposite effect on AR in prostate cells

https://www.ncbi.nlm.nih.gov/pubmed/23399562

if the same applies to penis tissue and going by this study on finasteride showing doubled AR expression in the penis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069023/

may be that could reverse androgen insensitivity?
if not at least it' can prevent someone with PFS from getting prostate cancer
I'm trying pioglitazone, I'll let you know
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capitalCK
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Re: FOUND THE CAUSE OF PSSD!!! SEROTONIN - PPARy - nNOS *REVEALED*

Unread post by capitalCK »

Did anyone make further progress on this? I actually arrived at this forum via the original blog post. Quoting relevant parts below:
Take DXM (dextromethorphan) or Memantine to upregulate the NMDA-receptors; to restore the Nitric Oxide pathway. [study 1] [study 2]
Easy to get over the counter.
Take Risperidone; an antipsychotic for 1-week to upregulate the Dopamine D2-receptors; as they are needed for erections etc [upregulation study] [D2 & Erections]
forskolin, choline, uridine, inositol and importantly a peptide BPC-157 also upregulates D2 receptors. So, perhaps can skip this anti-psychotic medication and use these instead?
Find a source and buy LECOZOTAN - a unique 5-HT1A antagonist which should block the post-synaptic receptors and restore nerve sensations and spinal connections.
Learned that CBG (not cbd) is also 5-HT1A antagonist. Perhaps that could be used.

This is assuming the original hypothesis is correct. But @TalkingAnt seems to think of something else. So, did anyone experiment and get any results with this protocol?
Halan
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Re: FOUND THE CAUSE OF PSSD!!! SEROTONIN - PPARy - nNOS *REVEALED*

Unread post by Halan »

capitalCK wrote: Thu Sep 10, 2020 9:54 pm Did anyone make further progress on this? I actually arrived at this forum via the original blog post. Quoting relevant parts below:
Take DXM (dextromethorphan) or Memantine to upregulate the NMDA-receptors; to restore the Nitric Oxide pathway. [study 1] [study 2]
Easy to get over the counter.
Take Risperidone; an antipsychotic for 1-week to upregulate the Dopamine D2-receptors; as they are needed for erections etc [upregulation study] [D2 & Erections]
forskolin, choline, uridine, inositol and importantly a peptide BPC-157 also upregulates D2 receptors. So, perhaps can skip this anti-psychotic medication and use these instead?
Find a source and buy LECOZOTAN - a unique 5-HT1A antagonist which should block the post-synaptic receptors and restore nerve sensations and spinal connections.
Learned that CBG (not cbd) is also 5-HT1A antagonist. Perhaps that could be used.

This is assuming the original hypothesis is correct. But @TalkingAnt seems to think of something else. So, did anyone experiment and get any results with this protocol?
Agmatine is a NMDA antagonist too and it increases NO synthase
Robalzotan is a 5-ht1a antagonist and I think it's easier to find than Lecozotan
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capitalCK
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Re: FOUND THE CAUSE OF PSSD!!! SEROTONIN - PPARy - nNOS *REVEALED*

Unread post by capitalCK »

Halan wrote: Thu Sep 10, 2020 10:21 pm Agmatine is a NMDA antagonist too and it increases NO synthase
Robalzotan is a 5-ht1a antagonist and I think it's easier to find than Lecozotan
From Examine:
Agmatine can also inhibit nitric oxide synthase enzymes, which allows it to regulate elevated levels of nitric oxide. Agmatine can inhibit calcium channels and certain serotonin receptors as well. Further research is needed to determine the full extent of agmatine’s mechanisms.
Sounds like Agmatine DECREASES synthase, not increases it.
And it also seems to increase serotonin sensitivity as it is antagonizing it.

Correct me if I'm misinterpreting it - I'm new to this.

Robalzotan - I think CBG oil is much easier to find and safer than a RX drug?
Halan
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Re: FOUND THE CAUSE OF PSSD!!! SEROTONIN - PPARy - nNOS *REVEALED*

Unread post by Halan »

capitalCK wrote: Thu Sep 10, 2020 10:29 pm
Sounds like Agmatine DECREASES synthase, not increases it.
And it also seems to increase serotonin sensitivity as it is antagonizing it.

Correct me if I'm misinterpreting it - I'm new to this.
Interesting that I read this part of agmatine page on Examine today. I thought: what a hell? I see everywhere people claiming it increases NO and pumps!

Well, this can be confusing.

Take a look. Ctrl + f "agmatine":
https://examine.com/nutrition/nitric-ox ... ansmitter/

"Agmatine is a very interesting, novel neurotransmitter. First of all, it activates production of nitric oxide via the alpha-2 adrenergic receptors more potently than arginine does, and is likely to be better for producing nitric oxide."
but...
"Agmatine has roles as an NMDA antagonist, a neuronal nitric oxide inhibitor (not related to "the pump" in any way), and a serotonin receptor signal enhancer, and is an activator of both alpha-2-adrenergic receptors and imidazoline receptors."

So, seems that in the brain it can inhibit NO.
Take a look on this response by Examine owner, silverhydra:

"There are three variants of NOS:

eNOS; endothelial NOS. Mostly related to blood flow.
iNOS; inducible NOS. Mostly related to inflammation.
nNOS; neuronal NOS. Mostly related to inflammation in the brain.
Agmatine inhibits nNOS but activates eNOS. It can improve blood flow but, at the same time, prevent support cells in the brain (glial cells) from causing excess oxidative damage to neurons thereby protecting them.

For all intents and purposes the three NOS variants are drastically different from one another and something that acts on eNOS provides no insight as it its actions on iNOS and nNOS; they're just too different.
"
https://old.reddit.com/r/Nootropics/com ... e/dpeq2ms/
capitalCK wrote: Thu Sep 10, 2020 10:29 pm Robalzotan - I think CBG oil is much easier to find and safer than a RX drug?
Yes, CBG is very easy to find on the internet.
But seems Robalzotan is more selective to 5-ht1a. I need to do more research on this.
I think CBG can do the trick, though. It's easy to find a CBG isolate extract.
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capitalCK
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Re: FOUND THE CAUSE OF PSSD!!! SEROTONIN - PPARy - nNOS *REVEALED*

Unread post by capitalCK »

Here:
Image

Looks like nNOS activates eNOS. So, we need both.
For PFS/PSSD, it seems to be that signaling from Dopamine-> nNOS -> eNOS is not functioning.
Atleast, that's what I think OP was trying to say.

Image
kali
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Re: FOUND THE CAUSE OF PSSD!!! SEROTONIN - PPARy - nNOS *REVEALED*

Unread post by kali »

Anyone has try yet???

Don't know how these meds (dextromethorphan, CBG, choline, uridine, inositol ) cure PSSD? cuz these all you can get over the counter?

So has anyone tried??

So confusing.....
Thomas
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Re: FOUND THE CAUSE OF PSSD!!! SEROTONIN - PPARy - nNOS *REVEALED*

Unread post by Thomas »

From what I read here, it seems that they give some relief to some people.
Sadly, as we do not have any scientific approach, this sentence could be used for almost anything, as the "some" are not quantified.
Escitalopram, 10mg/day, Jan-May 2019. Fluoxetine, May-Sept 2019. Mirtazapine 7,5mg/day, November 2019-January 2020. Escitalopram, 5mg/day, Feb-May 2020.
Symptoms: sexual & emotional numbness
Ch21
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Re: FOUND THE CAUSE OF PSSD!!! SEROTONIN - PPARy - nNOS *REVEALED*

Unread post by Ch21 »

I myself have no erection problems. The biggest problem is numbness.
Lokzo55
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Re: FOUND THE CAUSE OF PSSD!!! SEROTONIN - PPARy - nNOS *REVEALED*

Unread post by Lokzo55 »

If anyone tries CBG oil, please let me know!!! If this works anything like Cyproheptadine, this could be a very useful compound!!!
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