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5-ht1a receptor agonist or antagonist? Which one is our target?

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Guerrila V


I’m very confused about 5-ht1a receptors, and I think also a lot of people are confused. SSRI desensitizes these receptors, so why 5-ht1a antagonists, like WAY 100 635, are recommended? Receptors antagonist wouldn’t lead to more serotonin production?

Also 5-ht1a agonists are recommended to treat PSSD, like Ginkgo Biloba. In my logic, I think agonists should be more useful, as these recepetors are downregulated. Of course I’m not a specialist.

“With respect to serotonin, this journal states that serotonin exerts a stimulatory effect on sexual functioning when acting on 5-HT1A receptors and an inhibitory effect when it acts on 5-HT2/5-HT1B/5-HT1C receptors.” (I'd post the link but I can't cause I'm new here)

Jay, can you explain to us why this confusion? Thank you!

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Guerrila V wrote:I’m very confused about 5-ht1a receptors, and I think also a lot of people are confused. SSRI desensitizes these receptors, so why 5-ht1a antagonists, like WAY 100 635, are recommended? Receptors antagonist wouldn’t lead to more serotonin production?

Also 5-ht1a agonists are recommended to treat PSSD, like Ginkgo Biloba. In my logic, I think agonists should be more useful, as these recepetors are downregulated. Of course I’m not a specialist.

“With respect to serotonin, this journal states that serotonin exerts a stimulatory effect on sexual functioning when acting on 5-HT1A receptors and an inhibitory effect when it acts on 5-HT2/5-HT1B/5-HT1C receptors.” (I'd post the link but I can't cause I'm new here)

Jay, can you explain to us why this confusion? Thank you!

Serotonin does not stimulate "sexual functioning" with exception of the ejaculation aspect as 5-HT1A activation does decrease 'ejaculation latency'....that's an old journal entry you are quoting... A LOT of research has been conducted and CORRECTED since then.


Arrow http://www.ncbi.nlm.nih.gov/pubmed/19435548
Arrow http://www.ncbi.nlm.nih.gov/pubmed/1357709
Arrow http://www.ncbi.nlm.nih.gov/pubmed/11965359

1A agonists and activation of serotonin 1A decreases erections and the initiatory aspects of male sexual behavior as well as reducing the testosterone response to female pheromones....so no, 1A agonism is not recommended...it may help with trust and partner bonding but there are other, more plausible ways to add oxytocin than that receptor....


Int J Neuropsychopharmacol. 2009 Sep;12(Cool:1045-53. doi: 10.1017/S1461145709000406. Epub 2009 May 13.
5-HT(1A) receptor antagonism reverses and prevents fluoxetine-induced sexual dysfunction in rats.
Sukoff Rizzo SJ1, Pulicicchio C, Malberg JE, Andree TH, Stack GP, Hughes ZA, Schechter LE, Rosenzweig-Lipson S.
Author information
Abstract
Sexual dysfunction associated with antidepressant treatment continues to be a major compliance issue for antidepressant therapies. 5-HT(1A) antagonists have been suggested as beneficial adjunctive treatment in respect of antidepressant efficacy; however, the effects of 5-HT(1A) antagonism on antidepressant-induced side-effects has not been fully examined. The present study was conducted to evaluate the ability of acute or chronic treatment with 5-HT(1A) antagonists to alter chronic fluoxetine-induced impairments in sexual function. Chronic 14-d treatment with fluoxetine resulted in a marked reduction in the number of non-contact penile erections in sexually experienced male rats, relative to vehicle-treated controls. Acute administration of the 5-HT(1A) antagonist WAY-101405 resulted in a complete reversal of chronic fluoxetine-induced deficits on non-contact penile erections at doses that did not significantly alter baselines. Chronic co-administration of the 5-HT(1A) antagonists WAY-100635 or WAY-101405 with fluoxetine prevented fluoxetine-induced deficits in non-contact penile erections in sexually experienced male rats. Moreover, withdrawal of WAY-100635 from co-treatment with chonic fluoxetine, resulted in a time-dependent reinstatement of chronic fluoxetine-induced deficits in non-contact penile erections. Additionally, chronic administration of SSA-426, a molecule with dual activity as both a SSRI and 5-HT(1A) antagonist, did not produce deficits in non-contact penile erections at doses demonstrated to have antidepressant-like activity in the olfactory bulbectomy model. Taken together, these data suggest that 5-HT(1A) antagonist treatment may have utility for the management of SSRI-induced sexual dysfunction.
PMID: 19435548 [PubMed - indexed for MEDLINE]

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Flip!

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Now I'm confused. berberine is 5HT1A agonist or antagonist?

Flip!

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Flip! wrote:http://area1255.blogspot.ch/2014/09/natural-5-ht1a-receptor-antagonists.html?m=1
after writing I reread this page and I understood

Yes, it's PROPOSED that berberine is a autoreceptor agonist and post-synaptic antagonist..that means it reduces serotonin by autoreceptor activation and blocks the post-synaptic 1A receptors.

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Guerrila V wrote:I’m very confused about 5-ht1a receptors, and I think also a lot of people are confused. SSRI desensitizes these receptors, so why 5-ht1a antagonists, like WAY 100 635, are recommended? Receptors antagonist wouldn’t lead to more serotonin production?

Also 5-ht1a agonists are recommended to treat PSSD, like Ginkgo Biloba. In my logic, I think agonists should be more useful, as these recepetors are downregulated. Of course I’m not a specialist.

“With respect to serotonin, this journal states that serotonin exerts a stimulatory effect on sexual functioning when acting on 5-HT1A receptors and an inhibitory effect when it acts on 5-HT2/5-HT1B/5-HT1C receptors.” (I'd post the link but I can't cause I'm new here)

Jay, can you explain to us why this confusion? Thank you!

Remember, the serotonin 5-HT1A receptor has two sides.

-PRE-SYNAPTIC (say "left", pre-synapse,) AKA the SOMATODENDRITIC AUTORECEPTORS which DECREASE primarily, serotonin and GABA neuron firing as well as glutamate, to a lesser extent.   (activating this receptor can, in theory, enhance behavioral and emotional components of sexual behavior but mostly works on 'bonding' and 'passion' however the net result of decreased serotonin is increased sexual interest, this includes feelings of love and attachment)

NOTE : aggression is also DECREASED by the serotonin autoreceptors meaning INCREASED serotonin spikes aggression and hostility whereas DECREASED serotonin decreases certain forms of aggression - but it depends on the TYPE; as said; 'certain forms' of aggression...instrumental / objective oriented aggression relies on serotonin etc...

-POST-SYNAPTIC  5-HT1A receptors ; these are the ''bad'' serotonin 1A receptors; they block nitric oxide activity, decrease NMDA-gutamate activity and rapidly increase beta-endorphin release as well as cortisol and prolactin...all of these are negative 'anti-sexual' changes...

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Flip!

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ok now it's clear
thank you

Guerrila V


Area-1255 wrote:
Guerrila V wrote:I’m very confused about 5-ht1a receptors, and I think also a lot of people are confused. SSRI desensitizes these receptors, so why 5-ht1a antagonists, like WAY 100 635, are recommended? Receptors antagonist wouldn’t lead to more serotonin production?

Also 5-ht1a agonists are recommended to treat PSSD, like Ginkgo Biloba. In my logic, I think agonists should be more useful, as these recepetors are downregulated. Of course I’m not a specialist.

“With respect to serotonin, this journal states that serotonin exerts a stimulatory effect on sexual functioning when acting on 5-HT1A receptors and an inhibitory effect when it acts on 5-HT2/5-HT1B/5-HT1C receptors.” (I'd post the link but I can't cause I'm new here)

Jay, can you explain to us why this confusion? Thank you!

Remember, the serotonin 5-HT1A receptor has two sides.

-PRE-SYNAPTIC (say "left", pre-synapse,) AKA the SOMATODENDRITIC AUTORECEPTORS which DECREASE primarily, serotonin and GABA neuron firing as well as glutamate, to a lesser extent.   (activating this receptor can, in theory, enhance behavioral and emotional components of sexual behavior but mostly works on 'bonding' and 'passion' however the net result of decreased serotonin is increased sexual interest, this includes feelings of love and attachment)

NOTE : aggression is also DECREASED by the serotonin autoreceptors meaning INCREASED serotonin spikes aggression and hostility whereas DECREASED serotonin decreases certain forms of aggression - but it depends on the TYPE; as said; 'certain forms' of aggression...instrumental / objective oriented aggression relies on serotonin etc...

-POST-SYNAPTIC  5-HT1A receptors ; these are the ''bad'' serotonin 1A receptors; they block nitric oxide activity, decrease NMDA-gutamate activity and rapidly increase beta-endorphin release as well as cortisol and prolactin...all of these are negative 'anti-sexual' changes...

Well explained!
I still with some questions
Here in this longecity post, you said 5ht1a pre synaptic agonism is bad in long term
"5-HT1A agonism (pre-synaptic) can have it's benefits, namely in reducing excess serotonin - HOWEVER, after persistent agonism - it tends to de-sensitize, which then sends a flood of disinhibited serotonin to the post-synaptic 1A receptors which then can inhibit penile erection and can reduce sexual motivation....especially regarding arousal by female pheromones or presence!"
http://www.longecity.org/forum/topic/76890-serotonin-5-ht1a-receptor-and-male-sexual-function-motivation/

So, using something like Berberine long term is not good, right? It acts in presynaptic agonism and post antagonism. You used berberine to treat your pssd, don't?

I don't know how this 5ht1a pre synaptic downreg ocurred by ssri use. Maybe tons of presynaptic agonism lead to this?

Btw, I think a good combo is Shilajit + Gingko. Gingko seems to 'modulate' 5-ht1a, Shilajit seems to decrease serotonin in the brain, so this IN THEORY would lead to sensitization of these receptors. I'll try it!

Area-1255

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Guerrila V wrote:
Area-1255 wrote:
Guerrila V wrote:I’m very confused about 5-ht1a receptors, and I think also a lot of people are confused. SSRI desensitizes these receptors, so why 5-ht1a antagonists, like WAY 100 635, are recommended? Receptors antagonist wouldn’t lead to more serotonin production?

Also 5-ht1a agonists are recommended to treat PSSD, like Ginkgo Biloba. In my logic, I think agonists should be more useful, as these recepetors are downregulated. Of course I’m not a specialist.

“With respect to serotonin, this journal states that serotonin exerts a stimulatory effect on sexual functioning when acting on 5-HT1A receptors and an inhibitory effect when it acts on 5-HT2/5-HT1B/5-HT1C receptors.” (I'd post the link but I can't cause I'm new here)

Jay, can you explain to us why this confusion? Thank you!

Remember, the serotonin 5-HT1A receptor has two sides.

-PRE-SYNAPTIC (say "left", pre-synapse,) AKA the SOMATODENDRITIC AUTORECEPTORS which DECREASE primarily, serotonin and GABA neuron firing as well as glutamate, to a lesser extent.   (activating this receptor can, in theory, enhance behavioral and emotional components of sexual behavior but mostly works on 'bonding' and 'passion' however the net result of decreased serotonin is increased sexual interest, this includes feelings of love and attachment)

NOTE : aggression is also DECREASED by the serotonin autoreceptors meaning INCREASED serotonin spikes aggression and hostility whereas DECREASED serotonin decreases certain forms of aggression - but it depends on the TYPE; as said; 'certain forms' of aggression...instrumental / objective oriented aggression relies on serotonin etc...

-POST-SYNAPTIC  5-HT1A receptors ; these are the ''bad'' serotonin 1A receptors; they block nitric oxide activity, decrease NMDA-gutamate activity and rapidly increase beta-endorphin release as well as cortisol and prolactin...all of these are negative 'anti-sexual' changes...

Well explained!
I still with some questions
Here in this longecity post, you said 5ht1a pre synaptic agonism is bad in long term
"5-HT1A agonism (pre-synaptic) can have it's benefits, namely in reducing excess serotonin - HOWEVER, after persistent agonism - it tends to de-sensitize, which then sends a flood of disinhibited serotonin to the post-synaptic 1A receptors which then can inhibit penile erection and can reduce sexual motivation....especially regarding arousal by female pheromones or presence!"
http://www.longecity.org/forum/topic/76890-serotonin-5-ht1a-receptor-and-male-sexual-function-motivation/

So, using something like Berberine long term is not good, right? It acts in presynaptic agonism and post antagonism. You used berberine to treat your pssd, don't?

I don't know how this 5ht1a pre synaptic downreg ocurred by ssri use. Maybe tons of presynaptic agonism lead to this?

Btw, I think a good combo is Shilajit + Gingko. Gingko seems to 'modulate' 5-ht1a, Shilajit seems to decrease serotonin in the brain, so this IN THEORY would lead to sensitization of these receptors. I'll try it!

Hard agonism tends to 'desensitize' the receptors, Yes. Berberine is unlikely to desensitize though, because it isn't producing the same level of efflux and constant bombardment of the Receptors as with SSRI's ; thus BER (Berberine) is unlikely to Produce this Effect.

Yes, I've used Berberine.

Shilajit and Ginkgo is a good combo, but Ginkgo can work to Provoke certain forms of Psychosis and OCD since it antagonizes glycine and GABA actions.

Arrow http://www.ncbi.nlm.nih.gov/pubmed/12600688

Arrow http://www.ncbi.nlm.nih.gov/pubmed/14504293

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