Nitric Oxide Stack to Treat PSSD (Cure PSSD Protocol 2021)

This is a place to post research you have done on the topic along with your conclusions.
MindChanger
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Re: Nitric Oxide Stack to Treat PSSD (Cure PSSD Protocol 2021)

Unread post by MindChanger »

Dexmedetomidine facilitates the expression of nNOS in the hippocampus to alleviate surgery-induced neuroinflammation and cognitive dysfunction in aged rats (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343769/).

5-HT(1A)R-selective agonist 8-OH-DPAT and selective serotonin reuptake inhibitor (SSRI) fluoxetine downregulated hippocampal neuronal nitric oxide synthase (nNOS) expression, whereas 5-HT(1A)R-selective antagonist NAN-190 upregulated hippocampal nNOS expression. By assessing anxiety-related behaviors using the novelty suppressed feeding, open-field, and elevated plus maze tests, we show that mice lacking nNOS gene [knock-out (KO)] or treated with nNOS-selective inhibitor 7-nitroindazole (7-NI; i.p., 30 mg/kg/d for 28 d; or intrahippocampal microinjection, 16.31 microg/1.0 microl) displayed an anxiolytic-like phenotype, implicating nNOS in anxiety (https://pubmed.ncbi.nlm.nih.gov/20164327/).

5-HT uptake induces NO production from nNOS physically linked to SERT, through a calmodulin (CaM)-dependent mechanism. NO formed in association with 5-HT transport might, through cGMP and cGMP-dependent protein kinase (PKG), phosphorylate SERT, increasing its activity. nNOS, by engaging the cGMP-dependent pathway that enhances intrinsic SERT activity (8), allows for a continual homeostatic fine-tuning of 5-HT uptake according to the ambient extracellular 5-HT concentration: the higher it is, the more rapidly it will be removed. (https://www.pnas.org/content/104/19/7739).

By using [(3)H]5HT, it is reported here that 5HT binds to nNOS, but only when the enzyme is active and in a superoxide-dependent manner. This binding is prevented by DPI but not by L-NAME. The formation of 5HT-nNOS complex was shown to be very well correlated with the production of ROS by 5HT in the presence of nNOS. A mechanism involving nNOS only in its initial step is proposed to explain both the formation of 5HT-nNOS complex and the production of ROS observed in the presence of nNOS and 5HT (https://pubmed.ncbi.nlm.nih.gov/19191108/).

We speculate that NO regulates pLTF by modulating extracellular 5-HT accumulation near phrenic motor neurons. Thus, NO exerts dose-dependent regulation of the balance between opposing serotonergic receptors and their downstream kinases (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361021/).

Activation of cortical 5-HT3 receptor-expressing interneurons induces NO mediated vasodilatations and NPY mediated vasoconstriction (https://www.frontiersin.org/articles/10 ... 00050/full).

5-HT3 activation is reported to increase intracellular cGMP levels,77 which rises the question of how an ion channel could link with this system. Reiser has suggested cytosolic Ca2+ and NO as possible mechanisms. Again, by contributing to NMDA facilitation due to the resulting membrane depolarization, more prolonged effects on the Ca2+ concentration through 5-HT3 activation could be postulated. Furthermore, it is well known that NMDA directly enhances nNOS activity (https://www.sciencedirect.com/science/a ... 1109002118).

Episodic spinal 5-HT receptor activation is sufficient to elicit pMF by an NADPH oxidase-dependent mechanism, suggesting common mechanisms of ROS formation with AIH-induced pLTF.

(5-HT (2A)) receptors increase production of cyclic guanosine monophosphate (cGMP) in slices of rat frontal cortex (https://www.neurotransmitter.net/migrai ... P%20levels.).

Impaired Expression of Neuronal Nitric Oxide Synthase in the Gracile Nucleus Is Involved in Neuropathic Changes in Zucker Diabetic Fatty Rats with and without 2,5-Hexanedione Intoxication (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846497/).

Estrogen deficiency induces compensatory NOS production which may be related to decreases in muscle to collagen ratio in female rabbit genital organs (https://pubmed.ncbi.nlm.nih.gov/11494077/).

Interesting articles, quite relate to this thread.
Area1255_2021
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Re: Nitric Oxide Stack to Treat PSSD (Cure PSSD Protocol 2021)

Unread post by Area1255_2021 »

Thank You for that MindChanger...
MindChanger
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Re: Nitric Oxide Stack to Treat PSSD (Cure PSSD Protocol 2021)

Unread post by MindChanger »

Everyone really interested, read those studies. I'd recommend to read fully the first study: especially serotonin and anxiety parts. Link with ERK phosphorylation and CREB activity as well as 5HT1A and SERT connection looks really important here.

1. Neuronal nitric oxide synthase and affective disorders (https://www.sciencedirect.com/science/a ... 0117300493).
2. Role of ERK signaling in activity-dependent modifications of histone proteins (https://www.sciencedirect.com/science/a ... 081400046X).
3. ROS and ERK signaling facilitate epigenetic silencing and support the fact that subtle increase of ROS above basal level act as key cell signaling molecules (https://pubmed.ncbi.nlm.nih.gov/30954555/).
4. cAMP/PKA Agonist Restores the Fasting-Induced Down-Regulation of nNOS Expression in the Paraventricular Nucleus *https://synapse.koreamed.org/articles/1025822)
5. Both dexamethasone and cycloheximide, which completely inhibited the induction of the calcium-independent NOS activity, caused a 40-70% recovery in calcium-dependent NOS activity when compared with slices collected immediately after OGD (https://pubmed.ncbi.nlm.nih.gov/9886076/).
6. Decrease in surface expression of GLuN2B-containing NMDA receptor after reducing endogenous nNOS expression is responsible for reduced glutamatergic synaptic transmission, which may be involved in behavioral aberrations associated with ASD (https://www.frontiersin.org/articles/10 ... 00886/full).
MisterCharlie
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Re: Nitric Oxide Stack to Treat PSSD (Cure PSSD Protocol 2021)

Unread post by MisterCharlie »

Area1255_2021 wrote: Mon Nov 08, 2021 9:26 pm Thank You for that MindChanger...
Any thought about a replacement for cialis? Ill do my own search as well.
MisterCharlie
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Re: Nitric Oxide Stack to Treat PSSD (Cure PSSD Protocol 2021)

Unread post by MisterCharlie »

I dont have nearly as severe pssd as others on here, just fyi.

So I was having one or two orgasms a day, after 2 weeks on the nitric cycle but no cialis (too much side effects) but not that much improvement in genital sensation, and not feeling too good in terms of my health, nervous all the time, and definitely blurry vision the day of taking histidine. Ive been taking different vitamins to correct the bad feeling, vitamin C,D,E, phosphatidyl choline, and nothing worked until I took 4 pills of zinc (with fat so not to get nauseous) and 80% of my improvement went away for two days so far. My penis still looks bigger than post pssd tho. I looked up zinc deficiency and it causes Serotonin and Gaba to drop (sexual inhibitors). If large amounts of histidine causes a zinc deficiency then that would explain what I'm feeling and why the improvements stopped so drastically after zinc supplementation.

Ropinirole increased my libido and genital sensation for a week but is quite possibly the most toxic drug Ive ever taken. Bad heart and eye pain for 3 weeks afterward after a single 1/2 of a pill.

Waiting for my eyes to improve then might try Seroquel (also linked to eye problems) to antagonize the dopamine receptors and cause them to upregulate in the long term.
MisterCharlie
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Re: Nitric Oxide Stack to Treat PSSD (Cure PSSD Protocol 2021)

Unread post by MisterCharlie »

"Stimulation of NMDARs results in activation of neuronal nitric oxide synthase (nNOS), an enzyme catalyzing the formation of nitric oxides (NO) from L-arginine (Garthwaite et al., 1989). NMDARs are predominantly concentrated in the limbic system, a brain area that has close relationship with MDD, BPD and anxiety"

From MinderChangers 1st article, last post on affective disorders.

Something like clozapine, an NMDAR agonist, could increase nNOS?
Jaxx
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Re: Nitric Oxide Stack to Treat PSSD (Cure PSSD Protocol 2021)

Unread post by Jaxx »

Not sure how many can relate but l-histadine seems to make me more numb (mentally. In fact, although viagra works for me it also makes me a bit numb.
Area1255_2021
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Re: Nitric Oxide Stack to Treat PSSD (Cure PSSD Protocol 2021)

Unread post by Area1255_2021 »

MisterCharlie wrote: Thu Nov 11, 2021 5:30 am I dont have nearly as severe pssd as others on here, just fyi.

So I was having one or two orgasms a day, after 2 weeks on the nitric cycle but no cialis (too much side effects) but not that much improvement in genital sensation, and not feeling too good in terms of my health, nervous all the time, and definitely blurry vision the day of taking histidine. Ive been taking different vitamins to correct the bad feeling, vitamin C,D,E, phosphatidyl choline, and nothing worked until I took 4 pills of zinc (with fat so not to get nauseous) and 80% of my improvement went away for two days so far. My penis still looks bigger than post pssd tho. I looked up zinc deficiency and it causes Serotonin and Gaba to drop (sexual inhibitors). If large amounts of histidine causes a zinc deficiency then that would explain what I'm feeling and why the improvements stopped so drastically after zinc supplementation.

Ropinirole increased my libido and genital sensation for a week but is quite possibly the most toxic drug Ive ever taken. Bad heart and eye pain for 3 weeks afterward after a single 1/2 of a pill.

Waiting for my eyes to improve then might try Seroquel (also linked to eye problems) to antagonize the dopamine receptors and cause them to upregulate in the long term.
Once again, glad to hear you are getting results!!! Sorry about the side-effects.
Area1255_2021
Posts: 168
Joined: Sun Aug 15, 2021 4:45 pm

Re: Nitric Oxide Stack to Treat PSSD (Cure PSSD Protocol 2021)

Unread post by Area1255_2021 »

Any updates people???
Jcumbo
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Re: Nitric Oxide Stack to Treat PSSD (Cure PSSD Protocol 2021)

Unread post by Jcumbo »

I thought pomegranate juice is an antiandrogen it messes with
Alpha reductase either over expressing or under I can't remember, I'm not technical but what are your thoughts?
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