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Area-1255's Research on PSSD.

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1 Area-1255's Research on PSSD. on Mon Dec 01, 2014 10:09 am

Area-1255

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From our Main Article here, we can see there is a multitude or reasonings, contributors, genetic changes and changes in individual proteins that lead to the onset of PSSD; Post-SSRI-Sexual-Dysfunction.

There are a few things to take into consideration.


-Chronic elevation of cortisol due to SSRI use, and prolactin increases as well as possibly estrogen, throw sex hormones off whack and thus this represents a major pathway in which PSSD occurs; TESTOSTERONE AND PROGESTERONE DEFICIENCY.

-There is a persistent de-sensitization of pre-synaptic 5-HT1A serotonin receptors, which renders this receptor less sensitive to serotonin activation or blockade, because these are autoreceptors; that normally act to inhibit serotonin release, as well as the release of dopamine, glutamate and acetylcholine - it is likely this reason that contributes to a hypodopaminergic state , then the postsynaptic receptors induce cortisol and prolactin release, lowering testosterone and dopamine further in both men and women. With serotonin now less on the presynaptic side, it floods both these postsynaptic receptors and all other available receptors that also have contractile or anti-sexual effects.

-5-HT2A/2C complex is reduced in terms of receptor expression, and the hypo-dopaminergic state induced by 5-ht1A dysfunction, furthers this issue , and since 5-ht2C receptor (but not 5-ht2A) initiates oxytocin-induced sexual response - there is a general oxytocin deficiency or response deficiency induced by the chronic downregulation of this complex.

-5-HT3/4 receptors are receiving too much serotonin due to the lessering of the other receptors, and these receptors are highly contractile and cause both overstimulation and prolactin increases; both of which will lower sexual functioning, in terms of both libido , state of mind and vascular enabling.

-Dopamine receptor expression is decreased, and due to excessive post-synaptic inhibition by serotonin at multiple now enabled subtypes, we have that issue as well as a HYPO GLUTAMATERGIC state ....glutamate and histamine, as well as dopamine, all play positive roles in sexual response....

5-HT1A,5-HT6,5-HT1B,5-HT1D, all lower glutamate, histamine, acetylcholine, dopamine etc....these receptors receive more activity due to the presynaptic de-sensitization of 5-ht1A's, and the downregulation of the type 2 serotonin complex.....


**DOWNREGULATION OF SEROTONIN TYPE 2 IS NOT BAD IN ITSELF, THOUGH THE 2C IS IN A WAY, WE SHOULDN'T WORK TO RESTORE EXPRESSION OF THESE, BUT RATHER, WORK TO , ON A BROAD LEVEL, PICK UP WHERE WE LEFT OFF**


Questions will always be made in terms of why dopamine agonists don't work for everyone, one would theorize they would help, but without looking at all factors, and fixing the hormonal issue if it applies, they won't work, because dopamine receptors are under expressional/tonic control by sex hormones, especially free testosterone.

In addition, the 5-ht1A issues, especially the postsynaptic activation of, causes the inhibition of penile erection directly, and will block the effects of dopamine agonists of erectile responses.



Psychopharmacology (Berl). 1992;108(1-2):47-50.
5-HT1A receptor agonists prevent in rats the yawning and penile erections induced by direct dopamine agonists.
Simon P1, Guardiola B, Bizot-Espiard J, Schiavi P, Costentin J.
Author information
Abstract
The new compound (+) S-20499, an amino chromane derivative (8[-4[N-(5-methoxychromane-3yl)N-propyl]aminobutyl] azaspiro[4-5] décane-7,9 dione), is a high affinity full 5-HT1A agonist. We have investigated its effects on dopaminergic transmission. (+) S-20499 displayed a 10(-Cool M affinity for D2 dopamine (DA) receptors, 100 fold lower than for 5-HT1A receptors. The hypothermic effect of the drug was reversed by haloperidol in mice, suggesting that it behaves as a direct dopamine agonist. However, increasing doses of (+) S-20499 induced neither yawning nor penile erections, which constitute characteristic responses of direct DA agonists administered at low doses. In addition, (+) S-20499 prevented the apomorphine (100 micrograms/kg SC) induced yawning and penile erections. This inhibition appears to result from the stimulation of 5-HT1A receptors since it is an effect shared by both buspirone (from 5 mg/kg) and 8-OH-DPAT (from 0.10 mg/kg). In addition, when rats are treated with the 5-HT1A receptor antagonist tertatolol (2-5 mg/kg; SC), increasing doses of (+) S-20499 elicit the expected yawns and penile erections. It is concluded that the 5-HT1A agonist property opposes to that of D2 dopamine receptor stimulation with regard to yawning and penile erections.
PMID: 1357709 [PubMed - indexed for MEDLINE]

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2 Re: Area-1255's Research on PSSD. on Mon Dec 01, 2014 10:58 am

forexworld12

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Area-1255 Intelligence Oversight
Area-1255 Intelligence Oversight
Some more info on the causes of PSSD and related treatments written by Area-

5-HT1A downregulation is NOT going to cause libido issues directly, but indirectly because the PreSynaptic heteroreceptors inhibit serotonin release and function.   However, POSTSYNAPTIC 5-HT1A activation may cause sexual dysfunction.
Thus more serotonin is now floating around at 1B,1D,1F,2A,2C,3,4,5 as a result of presynaptic 5-HT1A downregulation, yet the postsynaptic 5-HT1A's induce prolactin, endorphin, cortisol, ACTH and oxytocin release.
Practically every serotonin receptor dampens the libido and sexual function.
Most prominently the 5-HT2A/2C Complex; as they play the neuroendocrine roles of inducing cortisol, ACTH and prolactin - all of which lower your testosterone. Transiently at the least; and accumulating. As time goes on this becomes more and more of an issue. Don't let anyone fool you into thinking SSRI-induced sexual dysfunction is easy to treat, it's not.  In fact, it's the one neuroendocrine disorder that is incredibly difficult to treat, and takes time. Even hormone replacement therapy may not fully blunt the effects of this disorder; PSSD included, and there are no direct remedies to address all symptoms off the bat.  

However, there is a combination of dietary techniques that can help reduce overall serotonin levels.
The first is raising histamine - which indirectly modulates serotonergic cell firing.

You can raise histamine by taking Vitamin B3 (Niacin), Vitamin B12, and Folate (but not methylfolate).

You can also add a product called "YAMOA" which is an H3 blocker and will induce neuronal histamine release.
A few others have been documented to contain H3 blockers as well - such as "Kutaj".

You should also be on a high-protein diet.

Modafanil would be good in this regard, if it hadn't been for the serotonergic 3A activation it causes.

In addition, using 5-HT2A antagonists; like Ketanserin, Trazodone or Remeron may help alleviate some of the vasoconstriction caused by SSRI use. They are commonly added as augmenters to SSRI's - and do indeed reduce some of the sexual sides.
Chamomile and Lysine combo may help as they block the 5-HT4's - which also have constricting effects - and are the one of the strongest stimulant receptors by serotonin.  

Zofran (an anti-emetic drug) and Ginger have 5-HT3 blocking effects - and may have minor benefits as the 5-HT3 receptor is also known to participate in prolactin release. (!) (!)

In addition, the 5-HT4 receptor and estrogen are linked. (!) By minimizing or reducing estrogen levels (by means of an AI in particular), less sex drive dampening prolactin is released. 5-HT4 antagonism alone induces some vasodilation, depending on how much serotonin is around the other receptors..(!)


In the meantime, Ginkgo Biloba seems to have a positive effect on SSRI-induced sexual dysfunction. (!)  It acts as a PDE-5 inhibitor (!) (!) and can boost acetylcholine and glutamate; two neurotransmitters positively associated with libido and sexual function, and the same mechanism by which serotonin causes some dysfunction. (!)

Yohimbine has also been used with SSRI-induced SD - with many showing significant improvement.

Yohimbine benefits users in two ways. (!)
1.) By blocking alpha-2-receptors; thus improving circulation and indirectly releasing nitric oxide,histamine and acetylcholine.
2.) By blocking multiple serotonin subtypes.

Yohimbine and Trazodone are also incredibly synergistic.(!) As yohimbine blocks 5-HT1B/1D/1F/2B serotonin receptors and trazodone blocks 5-HT2A serotonin and alpha-1-adrenergic receptors - all of which will inevitably improve all aspects of sexual function, including libido.

There are also natural compounds that can reduce serotonin levels (and not just receptors).

Panax ginseng & Vitex


http://area1255.blogspot.in/2014/06/4-natural-otc-serotonin-antagonists.html

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3 Re: Area-1255's Research on PSSD. on Mon Dec 01, 2014 11:45 am

Area-1255

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Admin / Head Writer
Admin / Head Writer
forexworld12 wrote:Some more info on the causes of PSSD and related treatments written by Area-

5-HT1A downregulation is NOT going to cause libido issues directly, but indirectly because the PreSynaptic heteroreceptors inhibit serotonin release and function.   However, POSTSYNAPTIC 5-HT1A activation may cause sexual dysfunction.
Thus more serotonin is now floating around at 1B,1D,1F,2A,2C,3,4,5 as a result of presynaptic 5-HT1A downregulation, yet the postsynaptic 5-HT1A's induce prolactin, endorphin, cortisol, ACTH and oxytocin release.
Practically every serotonin receptor dampens the libido and sexual function.
Most prominently the 5-HT2A/2C Complex; as they play the neuroendocrine roles of inducing cortisol, ACTH and prolactin - all of which lower your testosterone. Transiently at the least; and accumulating. As time goes on this becomes more and more of an issue. Don't let anyone fool you into thinking SSRI-induced sexual dysfunction is easy to treat, it's not.  In fact, it's the one neuroendocrine disorder that is incredibly difficult to treat, and takes time. Even hormone replacement therapy may not fully blunt the effects of this disorder; PSSD included, and there are no direct remedies to address all symptoms off the bat.  

However, there is a combination of dietary techniques that can help reduce overall serotonin levels.
The first is raising histamine - which indirectly modulates serotonergic cell firing.

You can raise histamine by taking Vitamin B3 (Niacin), Vitamin B12, and Folate (but not methylfolate).

You can also add a product called "YAMOA" which is an H3 blocker and will induce neuronal histamine release.
A few others have been documented to contain H3 blockers as well - such as "Kutaj".

You should also be on a high-protein diet.

Modafanil would be good in this regard, if it hadn't been for the serotonergic 3A activation it causes.

In addition, using 5-HT2A antagonists; like Ketanserin, Trazodone or Remeron may help alleviate some of the vasoconstriction caused by SSRI use. They are commonly added as augmenters to SSRI's - and do indeed reduce some of the sexual sides.
Chamomile and Lysine combo may help as they block the 5-HT4's - which also have constricting effects - and are the one of the strongest stimulant receptors by serotonin.  

Zofran (an anti-emetic drug) and Ginger have 5-HT3 blocking effects - and may have minor benefits as the 5-HT3 receptor is also known to participate in prolactin release. (!) (!)

In addition, the 5-HT4 receptor and estrogen are linked. (!) By minimizing or reducing estrogen levels (by means of an AI in particular), less sex drive dampening prolactin is released. 5-HT4 antagonism alone induces some vasodilation, depending on how much serotonin is around the other receptors..(!)


In the meantime, Ginkgo Biloba seems to have a positive effect on SSRI-induced sexual dysfunction. (!)  It acts as a PDE-5 inhibitor (!) (!) and can boost acetylcholine and glutamate; two neurotransmitters positively associated with libido and sexual function, and the same mechanism by which serotonin causes some dysfunction. (!)

Yohimbine has also been used with SSRI-induced SD - with many showing significant improvement.

Yohimbine benefits users in two ways. (!)
1.) By blocking alpha-2-receptors; thus improving circulation and indirectly releasing nitric oxide,histamine and acetylcholine.
2.) By blocking multiple serotonin subtypes.

Yohimbine and Trazodone are also incredibly synergistic.(!) As yohimbine blocks 5-HT1B/1D/1F/2B serotonin receptors and trazodone blocks 5-HT2A serotonin and alpha-1-adrenergic receptors - all of which will inevitably improve all aspects of sexual function, including libido.

There are also natural compounds that can reduce serotonin levels (and not just receptors).

Panax ginseng & Vitex


http://area1255.blogspot.in/2014/06/4-natural-otc-serotonin-antagonists.html

[b]
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EXCELLENT FOREX! Smile

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4 Re: Area-1255's Research on PSSD. on Fri Nov 20, 2015 7:04 am

Guerrila V


"You can raise histamine by taking Vitamin B3 (Niacin), Vitamin B12, and Folate (but not methylfolate)."

Why not methyl folate?

5 Re: Area-1255's Research on PSSD. on Fri Nov 20, 2015 3:00 pm

Area-1255

avatar
Admin / Head Writer
Admin / Head Writer
Guerrila V wrote:"You can raise histamine by taking Vitamin B3 (Niacin), Vitamin B12, and Folate (but not methylfolate)."

Why not methyl folate?

Methyl groups break down histamine.

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