84 replies to this topic

[Area-1255]

NATURAL 5-HT1A Antagonists/Agonists/Modulators

 

 

 

It seems some people may have overlooked the obvious in regards to serotonergic modulation and the subsequent nootropic effects.

 

Besides WAY 100,135, WAY 100,635 and Lecozotan, I may have found one other notable ingredient.

 

 

Ginkgo Biloba acts as an agonist / modulator of 5-HT1A receptor expression, whereas Berberine acts as a presynaptic only agonist of 5-HT1A's - while at the 5-HT1A postsynaptic (where it releases ACTH, cortisol, prolactin etc) it acts to inhibit. 

Thus berberine may be a useful tool not for increasing serotonergic neurotransmission through that pathway in particular, but for inhibiting excess serotonin and for reducing some of the negative neuroendocrine effects of serotonin. Notably, berberine also inhibited 5-HT2 type receptors and exhibited anxiolytic activity this way as well.

 

Berberine also inhibits PDE-5 mRNA - thus it may be the best natural tool for post and current SSRI-induced sexual dysfunction as well as in improving cognitive disturbances caused by serotonergic drugs.

 

http://area1255.blog...ntagonists.html

 

{ REFERENCE ONE }

 

 

 

The aim of this study was to assess the anxiolytic effect of berberine (abbrev. BER) using two experimental anxiety models in the mouse. In the black and white test of anxiety, berberine (100, 500 mg/kg) produced an increase in the first time entry, time spent in the white section, and total changes between two compartments. On the other hand, in the elevated plus-maze test, berberine (100, 500 mg/kg) produced an increase in the time spent and arm entries in the open arms, and a decrease in the time spent and arm entries in the closed arms. Berberine (500 mg/kg) decreased locomotor activity in mice. Furthermore, BER at 100, 500 mg/kg decreased concentrations of NE, DA and 5-HT, and increased the concentrations of VMA, HVA and 5-HIAA in the brain stem. BER also attenuated the anxiogenic effect of WAY-100635, 8-OH DPAT and DOI and enhanced the anxiolytic effect of BUS, p-MPPI and RIT in the elevated plus-maze. These results suggested that berberine at 100 mg/kg had a significant anxiolytic-like effect, which was similar to that observed with 1 mg/kg diazepam and 2 mg/kg buspirone. The anxiolytic mechanism of BER might be related to the increase in turnover rates of monoamines in the brain stem and decreased serotonergic system activity. Moreover, BER decreased serotonergic system activity via activation of somatodendritic 5-HT1A autoreceptors and inhibition of postsynaptic 5-HT1A and 5-HT2 receptors.

 

 

{ REFERENCE TWO }

 

 

 

 

 

OBJECTIVE:

To further investigate the action mechanisms of berberine (Ber) and to assess the effects of Ber on the mRNA expression of phosphodiesterase type 5 (PDE5) in rat corpus cavernosum.

METHODS:

After incubating with Ber for 1 or 3 h respectively, we examined the levels of PDE5 mRNA by reverse transcription polymerase chain reaction (RT-PCR).

RESULTS:

There were PDE5A1 and PDE5A2 mRNA expressions in the rat corpus cavernosum with PDE5A2 as the dominant isoform. Ber could obviously inhibit the mRNA expression of the two isoforms in the rat penis and bring on a pronounced decrease in PDE5A2 (P < 0.01).

CONCLUSION:

The present study indicates that the inhibitory effect of Ber on PDE5 mRNA expression, especially on PDE5A2, might account for its molecular mechanism for treating ED.

 

 

Edited by Area-1255, 10 September 2014 - 04:33 AM.

[medievil]

St johns worth upregulates 5ht1a, 5ht2a and 5ht2c thats why its been used by some ppl to reverse MDMA tolerance.

 

Chemical wise tandospirone is the strongest 5ht1a agonist and as effective as benzos for anxiety in high doses, and pindolol is a antagonist.

[Area-1255]

St johns worth upregulates 5ht1a, 5ht2a and 5ht2c thats why its been used by some ppl to reverse MDMA tolerance.

 

Chemical wise tandospirone is the strongest 5ht1a agonist and as effective as benzos for anxiety in high doses, and pindolol is a antagonist.

I was looking to show something natural though, to go beyond the normal range of thought.

[Area-1255]

Suprisingly, Creatine has action at 5-ht1a:

http://www.ncbi.nlm....pubmed/23352985

"These results indicate that the antidepressant-like effect of creatine is likely mediated by an interaction with 5-HT1A receptors. Of note, the present results also indicate that creatine improves the effectiveness of the selective serotonin reuptake inhibitors, a finding that may have therapeutic implications for the treatment of depressive disorders."

 

Ginger:

http://www.ncbi.nlm....pubmed/20363635

"In addition, the intestinal absorption of gingerols and shogaols was simulated and their interactions with P-glycoprotein were measured, suggesting a favourable pharmacokinetic profile for the 5-HT(1A) active compounds."

 

 

Sodium Butyrate, which is a natural byproduct of intestinal bacteria so you could take things like soil-based probiotics along with resistant starch, soluble fiber, other prebiotics, or even substances to improve the alkalinity of the intestines in order to promote proper bacterial growth.

http://www.sciencedi...16643280800497X

"5-HT_1A antagonist, WAY 100635, significantly block the antidepressant-like effects induced by NaB (Sodium Butyrate) plus EB. The mRNA expression of the serotonin-1A [5-hydroxytryptamine 1A (5-HT_1A)] receptor was increased in the co-treated group in hypothalamus, while there was no difference in the mRNA expression of 5-HT_2A or 5-HT_2C."

 

 

Cannabidiol, so vaporizing medical cannabis would work:

http://www.ncbi.nlm....pubmed/16258853

"Cannabidiol (CBD) is a major, biologically active, but psycho-inactive component of cannabis. In this cell culture-based report, CBD is shown to displace the agonist, [3H]8-OH-DPAT from the cloned human 5-HT1a receptor in a concentration-dependent manner. In contrast, the major psychoactive component of cannabis, tetrahydrocannabinol (THC) does not displace agonist from the receptor in the same micromolar concentration range. In signal transduction studies, CBD acts as an agonist at the human 5-HT1a receptor as demonstrated in two related approaches."

 

 

more Ginkgo evidence:

http://onlinelibrary...3802.x/abstract

"Investigation of [³H]8-hydroxy-2(di-n-propylamino)tetralin binding to 5-HT_1A receptors in cerebral cortex membranes of Wistar rats showed that the maximal number of binding sites (B_max) was reduced significantly (22%) in aged (24-month-old) as compared with young (4-month-old) animals. Chronic treatment with Ginkgo biloba extract did not alter binding in young rats but increased binding density significantly (33%) in aged rats."

Wow, very nice man! I can't believe I missed creatine all this time, I've studied it fairly thoroughly, considering it's one of my main sups for working out - must not have read thoroughly enough though. xD
Thanks!

 

Seems like creatine is probably a 5-HT1A autoreceptor antagonist...considering it "enhances" the efficacy of anti depressants.

Although 5-HT1A's are garbage altogether imo, I think blocking them generally makes more sense. 

The only serotonin receptor that seems to have any positive effects on endocrine system seems to be 5-HT7 ( a cAMP booster ).

 

Certainly, lower serotonin is good for working out and for hormones. 

You would have higher testosterone, lower cortisol and prolactin etc with lower serotonin.

 

 

Also higher nitric oxide, dopamine and other amino's with lower serotonin. 

Only downside is possibly an exaggerated stress response in some situations...although this could happen with elevated serotonin too.

[medievil]

Cannabis has too many widespread effects to use it as a 5ht1a ligand.

[Area-1255]

Cannabis has too many widespread effects to use it as a 5ht1a ligand.

My thoughts exactly, hence why I drifted away from it in listings.

Creatine has quite a nice overall pharmacological pathway thought.

 

-Increases DHT

-Methylator

-Increases Serotonin (or AutoR Blocker)

-Increases FTP (FastTwitchProtein)

-Might slightly decrease Myostatin

 

http://www.muscleand...ostatins-enemy/

http://www.ncbi.nlm....pubmed/19741313

http://forum.bodybui...php?t=146155983

[Area-1255]

From what  I understand the beta adrenergic and other positively coupled adl cyclase receptors have a pronounced effect on 5-HT1 systems, and second messengers play a role in controlling serotonergic firing.

[Area-1255]

Updated article with another berberine reference; showing it as a dual 5-ht1a modulator, 2a antagonist and a super potent 5-ht4 antagonist as well as a pde-5 inhibitor

[normalizing]

updated what article? you could have posted this information on the thread instead of saying "update!!!"

[Area-1255]

updated what article? you could have posted this information on the thread instead of saying "update!!!"

Well I can see why you're in the neg. ^_^

Please remember to bring common sense next time.

Edited by Area-1255, 07 October 2014 - 12:07 PM.

[stan08]

There's also agmatine and it's effect on 5-HT(1A/1B) receptors. 

 

http://www.ncbi.nlm....pubmed/18717332

"These results indicate that regulation on 5-HT1A/1B and alpha2 receptors, and activation AC in the frontal cortex is one of the important mechanisms involving in agmatine's antidepressant-like action."

 

I know it works great for me with reducing stress, anxiety and improving mood (not to mention the relief in lower back pain).

Edited by stan08, 07 October 2014 - 12:36 PM.

[lourdaud]

IME, butyric acid works very well as a 5-HT1A agonist. I bought mine from http://www.biocare.c...mGroupGuid=154 

Unfortunately I get insane insomnia from any 5HT1A agonist..

[Area-1255]

IME, butyric acid works very well as a 5-HT1A agonist. I bought mine from http://www.biocare.c...mGroupGuid=154 

Unfortunately I get insane insomnia from any 5HT1A agonist..

Me too, same reason why there are side-effects from cocaine, yohimbine, amphetamine etc.. indirect serotonin 5-HT1A activation can have an extremely potent euphoric and stimulant effect, it's responsible for addictive properties of many drugs...most people think that it's all dopamine - but in reality, it's the endorphin rush and signaling cascade leading to it that gives euphoria. 5-HT1A, serotonin 5-ht2A , 5-ht3 , and alpha-1-adrenergic receptors are all facilitator's of local / endogenous endorphin/enkephalin release. 

This also explains the effect of psuedoephedrine , not completely, but partly...same with epi shots.. and also..when you block/antagonize alpha-2's you get more indirect 5-ht1a agonism..unless alpha 1's are also blocked.

[normalizing]

still not seeing that article...

[Area-1255]

still not seeing that article...

It's right in the original post, in big blue hyperlinked writing, how could you miss it?

If you are ingesting or smoking psilocybin, just tell me now..then I will say I understand...

[normalizing]

for october you have article how to encounter ebola when it hits...

all you could have done is post direct link to the berberine article but noooo, you have to give hard time

[Area-1255]

for october you have article how to encounter ebola when it hits...

all you could have done is post direct link to the berberine article but noooo, you have to give hard time

The berberine article is in the original post..you're surfing through the blog feed on a cycle of delirium,..

[normalizing]

mind you, its horribly designed blog. all those trippy colours and confusing layout with shitload of ads, clearly you been on drugs

[Area-1255]

mind you, its horribly designed blog. all those trippy colours and confusing layout with shitload of ads, clearly you been on drugs

I disagree, and clearly so do many others...

[Area-1255]

mind you, its horribly designed blog. all those trippy colours and confusing layout with shitload of ads, clearly you been on drugs

lol again @ this.

[Flex]

I would appreciate any suggestions for postsynaptic 5-ht1a inhibitors or even longterm modulators like antipsychotics & etc.

or where to obtain Spinosin

--------------------------------

 5-ht-1a agonists i.e. inhibitors of Serotonine release:

 

Anxiolytic activity of Nymphaea alba Linn. in mice as experimental models of anxiety
http://www.ncbi.nlm....les/PMC3062121/

 

Effect of chronic Albizzia julibrissin treatment on 5-hydroxytryptamine1A receptors in rat brain
http://www.sciencedi....com/science/ar... 5705001115

 

Alkaloids from Eschscholzia californica and their capacity to inhibit binding of [3H]8-Hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A receptors in Vitro.
http://www.ncbi.nlm....pubmed/16562853

 

Anxiolytic-Like Effects of Chrysanthemum indicum Aqueous Extract in Mice: Possible Involvement of GABAA Receptors and 5-HT1A Receptors
http://www.ncbi.nlm....les/PMC3762266/

 

Search suggestion: look for e.g. "5-ht1a + herb + anxiolytic" because everything that decreases Serotonine is anxiolytic.

See pssdforum.com:

Natural compounds with 5-ht1a/Serotonine interacting properties

http://www.pssdforum....php?f=20&t=284

---------------------------------

 

Postsynaptic 5-ht1a antagonists:

 

Seems that the semen of Ziziphi spinosa exert an antagonist effect on postsynaptic 5-ht1a receptors

 

Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital-induced sleep may be related to postsynaptic 5-HT(1A) receptors.

http://www.ncbi.nlm....pubmed/20171860

 

On the other hand, this study couldnt confirm the effects at least a a low dose

Interactions of Magnolia and Ziziphus extracts with selected central nervous system receptors

A previous study demonstrated an interaction between a Ziziphus seed extract (drug extract ratio of 7.3:1) and the serotonin receptor subtypes 5-HT1A and 5-HT2 with a concentration of 10mg/ml (Liao et al., 1995).

This study did not duplicate those results.

However ZE in this study was tested at a concentrations100 times lower than the previous study, which is closer to that expected in the human body following traditional use.

http://www.nextpharm...tol_JEP2009.pdf

 

Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor.

The black cohosh 40% 2-propanol extract inhibited [(3)H]lysergic acid diethylamide (LSD) binding to the human 5-HT(7) receptor (IC(50) = 2.4 +/- 0.4 microg/mL) with greater potency than binding of [(3)H]-8-hydroxy-2-(di-N-propylamino)tetralin to the rat 5-HT(1A) receptor (IC(50) = 13.9 +/- 0.6 microg/mL)

http://www.ncbi.nlm....pubmed/12952416

---------------------------------------------------

You may ask for what its worth to inhibit postsynaptic 5-ht1a receptors:

 

- Subsequent binding studies were carried out using 5-HT(1A) and 5-HT(7) receptors because of their association with the hypothalamus, which has been implicated in the generation of hot flashes

- Anxiolytic effects

- (My personal assumption) : (could) decrease ones too social biases

- postsynaptic 5-ht1a interacts with presynaptic 5-ht1a receptors. From my understanding, its inhibition would decrease the release of Serotonine:

 

....but more important, local infusion of 1 microM WAY 100.635 into the amygdala now failed to augment the effect of citalopram. Both the flesinoxan and WAY 100.635 data suggest an involvement of postsynaptic 5-HT(1A) receptor-mediated feedback in the amygdala, which diminishes following chronic citalopram treatment.

Acute and chronic effects of citalopram on postsynaptic 5-hydroxytryptamine(1A) receptor-mediated feedback: a microdialysis study in the amygdala.

http://www.ncbi.nlm....pubmed/11259482

 

I´ve read this in a different paper with actually an opposite statement but its a pain in the ass to find it, though dont believe anything until the presentation of references.

--------------------------

Altough off-topic but relevant for the PSSD thing:

Berberine and evodiamine influence serotonin transporter (5-HTT) expression via the 5-HTT-linked polymorphic region.

http://www.ncbi.nlm....pubmed/21647174

Both berberine and evodiamine, alone and in combination, increased 5-HTT mRNA and protein expression significantly across the various alleles. When tested against the S, XS(11), L(G), L(A), XL(17), and XL(18) alleles, respectively, 100 μM berberine increased 5-HTT promoter activities by 67%, 128.7%, 106.9%, 100.4%, 26.2% and 82%, 2 μM evodiamine increased 5-HTT promoter activities by 216.7%, 81.6%, 305.6%, 181.5%, 175.3% and 102.2%. Berberine and evodiamine increased 5-HTT promoter activity differently depending on the genetic variation of the 5-HTTLPR polymorphism.

Edited by Flex, 07 April 2015 - 07:15 PM.

[normalizing]

flex, i appreciate your work and contributing to this forum, but can you please stop using chinese names for plants. their names for plants are as accurate and reliable as their products, full of lead, mercury and various toxins. to put simply, complete joke!

[Area-1255]

flex, i appreciate your work and contributing to this forum, but can you please stop using chinese names for plants. their names for plants are as accurate and reliable as their products, full of lead, mercury and various toxins. to put simply, complete joke!

You know what me and Flex have in common? We both have some correctly placed pragmatism and have a lot of research in our heads and elsewhere! Even "quickly"  accessible, but you...you just like to troll - you don't deserve a response from flex. I'm done dealing with you as well = every single thread I post you feel the need to hijack with illogical criticism, you don't have the guts or resources to even dispute the science - so instead you attack with ad hominems and assault on the elements of the thread. 

 

The fact that you deliberately look for these things tells me that either you are an {enemy} or former critic of Area-1255 ; our blog and  / or our writers - possibly from another forum, or that you simply want to be me and so you post your dribble in every topic I post. 

 

Now why don't you stop criticizing and start reading? 

Edited by Area-1255, 08 April 2015 - 06:24 PM.

[normalizing]

area-1255, you might be the smartest guy on the planet, i havent bothered to research that yet, but fact is, i ignore you mostly and i dont want to have to do anything with you and i was speaking to flex. if flex decides to respond, thats fine, if not, ill die of misery!

[Area-1255]

area-1255, you might be the smartest guy on the planet, i havent bothered to research that yet, but fact is, i ignore you mostly and i dont want to have to do anything with you and i was speaking to flex. if flex decides to respond, thats fine, if not, ill die of misery!

Yeah well, you can stop with the neg's / down-voting now though.

[Flex]

I´m too exhausted for this but I´ll try it anyway:

 

@ Area

 

Look if its about me I would stop posting months ago.

Because theres seemingly no great response no thank You or whatsoever to at least some valuable posts or to my intentions like: my post is absolutely senseless but it was well-meant.

 

I´m struggling a bit with it because my ego and/or my reward depends actually on this i.e. its my fuel.

But my beliefs (God) and ideology keep me going.

 

@ all

I found You (normalizing) as a not bad person and believe that You have some reasons to be e.g. sceptic.

 

When my depression occured I had lesser tolerance and was able to be more nervous, angry, even more blown away and to.. hate more. The emotional feedback, which brought me usually back on track, was dimmished.

I´ve disapointed myself but had at the same time the insight about the implication of biochemistry and behavior, so I begun to develop understanding for my self even when no one had any for me because they

didnt understood my reactions and perhaps even not their own in a certain sense.

 

 

-> I dont want to point on You out as someone damaged who should get compassion !

Its basically to keep that in mind when generally dealing with others i.e. possible reasons of the reaction and try to understand the point of the other

It could be the case for You in the remotest sense like above but of course it dont have to, its just a example how complicated causes could be.

Also not saying that love and compassion can heal the world( I´m no hippie ) but it could be used more often than You all think even to yourselves.

( Btw theres a Yugoslavian folk wisdom: nice words open heavy doors)

- e.g.:  everyone, male and female has a inner child but could get very fast ashamed of that, ergo they seem to me to be not grounded .. anyway I may be mistaken

-  for me is a simple smile sometimes the last thing what reminds me of humanity

 

- I couldnt find anything in You, e.g. being a sociopath, that makes me to respond just briefly, beeing careful &etc.

 

This is it. My response and the consequences from this could be detrimantal on my appearance i.e. pseudo-smart,brainwashed & whatever but I couldnt do it better.

And Yes, I have also bad sides like everyone else and sometimes bad nerves, wrath and so on..

------------------------

 

The pollution of the chinese herbs could be problematic because no one can tell which chinese company controlls the quality of their herbs.

Theres nevertheless the advantage in regards of interresting mechanisms where synthetic compounds arent able to do so

+ the investigation of research compounds can be halted so if You experience any negative efects, You cant know the reason because of the lack of studies.

 

Example: It seems to me that herbal compounds are able to be a mixed presynaptic 5-ht1a agonist and postsynaptic 5-ht1a antagonist (or solely one of these)

the development of a research compound for this case is complicated because the receptors are both too similair to get affected seperately.

(please dont ask me for refferences. due to google, its sometimes a pain)

 

You could nevertheless look into the products of known brands to find maybe something. In this case:

Planetary Herbals, Albizia Calm

but I doubt that theres a product for not well known herbs

 

I personally will keep on with them because I believe that the positive overweights the negative ( + some herbs dampens the effect of pollutants; leumbo nucifera is a cadmium scavanger)

and I´m trying to reduce it by choosing the big chinese brands.

Edited by Flex, 09 April 2015 - 05:30 PM.

[Area-1255]

I´m too exhausted for this but I´ll try it anyway:

 

@ Area

 

Look if its about me I would stop posting months ago.

Because theres seemingly no great response no thank You or whatsoever to at least some valuable posts or to my intentions like: my post is absolutely senseless but it was well-meant.

 

I´m struggling a bit with it because my ego and/or my reward depends actually on this i.e. its my fuel.

But my beliefs (God) and ideology keep me going.

 

 

I was addressing normalizing and his behavior on this forum - it's been consistently disruptive . 

[Flex]

I know, I was adressing the people in general with their non-response & etc. Therefore, even if I would consider Normalizings behavior as too negative aainst me, I would try to answer anyway. Just my own point.

 

@ Normalizing: You may know allready the following,.. anyway:

Some people tend to percieve Your response just as rough, because they see what they see on the first glance.

As said, nice words open heavy doors, it could be a win-win.

 

I would try to balance the response just for one or two steps down, and this just for the fallacy´s sake.

i.e. it wasnt someones intention to produce an certain impression with his post, neither You´re actually doing this but You sound more pissed than the others and this leads back to the first glance thing..

 

Otherway arround:

Step1:

so You do respond very pissed to a comment ?

Do You get allways easily pissed ? Yes ?  then I know Your weak points i.e. the buttons I have to press.

If You dont show how to get pissed, I wont know them.

 

Step2: You can get ..dunno.. annoyed instead of pissed or note it in a regardless/careless manner to get a "lotus effect"

 

(-> a trick to "trick Yourself" (e.g. dissociaction of feelings) doesnt pops up in my mind at the moment, but will post if I dont forget and if You like)

 

This has the advantage that altough I pissed You, I can expect that You will payback any time and I will in turn translate it into a weakpoint.

-> no immediate response, no eventuall response = no weakpoint.

Flex Your Mind

 

Just my suggestion.

 

And think of religion if You believe, it may help. Everything comes back either here or in the afterlife.

I for my self try therefore to not escalate things. Chin up

 

Edited by Flex, 09 April 2015 - 10:52 PM.

[Metagene]

flex, i appreciate your work and contributing to this forum, but can you please stop using chinese names for plants. their names for plants are as accurate and reliable as their products, full of lead, mercury and various toxins. to put simply, complete joke!

 

I don't have anything against you normalizing but this is getting ridiculous. There is nothing objectively wrong with the Chinese names.