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Natural 5-HT1A Agonists/Antagonists (PSSD,and Cognitive Function)

ginkgo biloba berberine natural 5-ht1a agonists antagonists 5ht1a antagonist natural herbal natural serotonin blocker pssd

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#61 Area-1255

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Posted 04 May 2015 - 08:14 AM

looove this thread!

Thanks.  :)


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#62 normalizing

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Posted 06 May 2015 - 10:04 PM

here is a very new article on zinc and glutamate; http://www.medicalne...ases/293472.php


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#63 Area-1255

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Posted 06 May 2015 - 11:17 PM

here is a very new article on zinc and glutamate; http://www.medicalne...ases/293472.php

Well now that's a new egg on your part, something that stands a useful contribution!

It also reinforces my earlier statement that Zinc is an NMDA antagonist. 


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#64 pinnacle

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Posted 13 May 2015 - 02:31 AM

I personally love Buspirone for treatment of anxiety, nothing else has ever worked nearly as effectively. So I must be one of the good responders to 5-HT1A activation.

 

Found a couple of interesting articles:

http://blogs.scienti...-bring-mood-up/

 

http://psychopharmac...ht1a-receptors/



#65 pinnacle

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Posted 13 May 2015 - 03:02 AM

I personally love Buspirone for treatment of anxiety, nothing else has ever worked nearly as effectively. So I must be one of the good responders to 5-HT1A activation.

 

Found a couple of interesting articles:

http://blogs.scienti...-bring-mood-up/

 

http://psychopharmac...ht1a-receptors/

 

I might add to this I also take Mirtazapine which has 5-HT2A antagonism properties and works wonderfully as an anti-depressant where others didn't, perhaps the combination of 5-HT1A (partial) agonism and blockade of 5-HT2A receptors is where the magic works  ;)



#66 normalizing

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Posted 13 May 2015 - 06:48 AM

burpirone is fucking weird. you really dont get any side effects from it? i used to get major dizzyness from just 2 pills 10mg. taken at night causes serious sleep problems too. i read combo with melatonin is somehow synergetic and possibly neurogenic, BUT dear lord, is it trippy to sleep on those two. you feel real weird, cant really pass out at all. its some weird sedating stimulating sensation that i havent felt from anything yet!


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#67 pinnacle

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Posted 14 May 2015 - 01:15 AM

burpirone is fucking weird. you really dont get any side effects from it? i used to get major dizzyness from just 2 pills 10mg. taken at night causes serious sleep problems too. i read combo with melatonin is somehow synergetic and possibly neurogenic, BUT dear lord, is it trippy to sleep on those two. you feel real weird, cant really pass out at all. its some weird sedating stimulating sensation that i havent felt from anything yet!

 

Not to get too off-topic; but I seem to be void of these side-effects a lot of users report. No brain zaps/dizzy spells. Or they subsided very quickly after week one. If anything I noticed slightly improved sleep by means of quicker onset to fall asleep. It's main positive mechanism for me has been a feeling of being at-ease around people and less impulsive. Am currently on the maximum dose of 60mg/day. I use melatonin too and am aware of the recent studies referring to some neurogenesis with this unique combination of Buspar + Melatonin. If anything, slightly increased anti-depressant effects that the Buspirone alone doesn't bring.

 

Probably an off-the-mark speculation: but I used to be an avid user of MDMA in my youth so I wonder if this somehow re-sparked those burned out/desensitised receptors, however I can't speak from expertise on this.

 

It also greatly assisted with the recovery from a reckless tianeptine dosing schedule that got out of hand and I ended up with some minor PAWS for a week or two. Won't be making that mistake again.  :)

 

Interesting about the disturbed sleep you report.



#68 normalizing

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Posted 14 May 2015 - 04:18 AM

can you elaborate more on the crazy tianeptine dosing schedule? were you using real high doses quite frequently and developed tolerance? and what is PAWS?

 

also, how long have you been taking buspirone regularly to push the dose so high as 60mg? thats insane for me. perhaps i should have used real low doses for few weeks slowly increasing dose and maybe getting used to it without suffering side effects.

i assume you take it in the morning and then melatonin at night right?

 

and yes, even melatonin didnt help with the sleep probs caused by buspirone. perhaps i made unwise choice using buspirone before bed? perhaps its best suited morning, throughout day.

 

and yes, i can see association with MDMA as i have abused it too at one point and the feeling of uneasyness falling asleep on MDMA is exactly the same as buspirone except zero euphoria.



#69 pinnacle

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Posted 14 May 2015 - 04:50 AM

Well tianeptine started off as life-changing for me, I became the most outgoing, energetic version of myself. Especially that initial morning dose, I was always up and ready for the day immediately afterwards. However, I allowed myself to get a bit sloppy and stopped using a scale and gradually got to the stage where I was scooping the powder willy nilly thinking there'd be no consequence; needless to say when I ran out I found out the hard way how terrible it was to suddenly cease this drug after using higher doses (I estimate ~100mg/day). Let it be a warning, opiate withdrawals are no fun. I was sleepless, restless, extremely irritable and felt like I had an ongoing flu and no energy. It's not to say tianeptine is evil, just that the line between therapeutic and abusive was a matter of inaccurate dosing. "The dose makes the poison".

 

With the buspirone I was on 10mg a day for the first two weeks before tapering up by 5mg at a time, every 3 days. Until reaching this point to which I found the maximum benefit at 20mg/3 x daily. Under a doctor's supervision of course.
You might be right about the evening dose affecting sleep, but I haven't made that association, although I'll see if I take it earlier in the day whether it changes things. I was always under the impression it was benefiting my sleep, but I might just be an unusual case where I don't seem to get the side effects so many report. I really enjoy the stuff, it had a "feel good" factor for a few weeks, which has stabilized now. But it still brings a calm and a smile which I like, especially if I'm already on edge before I take my next dose. I wonder if people give up on it too early?



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#70 normalizing

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Posted 15 May 2015 - 08:11 AM

yeah i wasnt doing buspirone regularly for a week. just on and off few days a week.

btw didnt you develop tolerance to tianeptine with such high doses? also, i tried the cheaper powder versions, they were not the same as the pharmaceutical pills. somehow, they felt similar BUT less potent generally, and also bad for the liver. dunno, just not the best quality perhaps hence why sold so cheap in bulk?



#71 SerP3nT

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Posted 15 May 2015 - 11:46 AM

i hate tianeptine personally. made me feel drowsy and all trance like all day.



#72 normalizing

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Posted 16 May 2015 - 06:56 AM

all day? it has such a short half life hence why it has indication to redose through the day. but i assume you should have taken it at night, not day, for drowsyness not to be a problem


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#73 SerP3nT

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Posted 21 May 2015 - 10:30 AM

yea mofo, all day


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#74 pinnacle

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Posted 23 June 2015 - 12:05 PM

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..

 

Wait, is Sodium Butyrate a 5-HT1A agonist or antagonist? Or inverse/partial? Please clarify. I can't seem to find much on this. 

Interestingly, though... Check this article:

Butyric Acid: an Ancient Controller of Metabolism, Inflammation and Stress Resistance?

#75 William Sterog

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Posted 23 June 2015 - 12:38 PM

What is your opinion about Uncaria rhynchophylla?

 

 When looking at the level of the receptors, geissoschizine methyl ether is a potent agonist of the 5-HT1A receptors while it is inhibitory at the 5-HT2A, 5-HT2C, and 5-HT7 receptors at the same concentration range, with the possibility of being a partial agonist at higher doses. This profile is very similar to the anti-psychotic drug Aripiprazole.

 

 

 

Geissoschizine methyl ether is an alkaloid in uncaria rhynchopylla which acts on the 5-HT1A receptors. It is able to outcompete 8-OH-DPAT binding to the receptor with an IC50 and Ki value of 904nM and 517nM (respectively) and activated the receptor in the contration range of 0.1–100μM (although it had 40% the potency as serotonin itself);[6] this has been noted elsewhere, where a Ki value of 800nM was reported for 5-HT1A receptors[42] and an EC50 in activating them was measured at 4.6+/-7μM, reaching maximal activation (Emax) of 85+/-3% the potency of 1μM serotonin.[43]

There appears to be affinity for 5-HT2C (Ki 900nM)[42] which was later found to be inhibition, possessing an IC50 of 5.07+/-0.41μM[43] although higher concentrations (20μM) have weak activating abilities suggesting it is a partial agonist.[43]

There appears to be affinity for 5-HT2A (Ki 1.4μM)[42] which was later noted to be inhibition; IC50 value of 4.87+/-0.44μM[43]and again higher concentrations (20μM) were noted to be weak agonists (and thus it was a partial agonist).[43]

5-HT7 is also inhibited with an IC50 of 610+/-290nM (blocking serotonin binding)[43] and 340nM (blocking LSD binding)[44]while the ability of geissoschizine methyl ether to block serotonin induced cAMP production is slightly weaker (IC50 6µM).[44]

Corynoxeine, isocorynoxeine, rhynchophylline, and isorhynchophylline fail to interact with the 5-HT1A receptor up to 100µM while hirsuteine and hirsutine were weakly effective (blocked 40% of 8-OH-DPAT binding at 100µM while geissoschizine methyl ether was absolute at 10µM).[6] When testing the overall Yokukansan plant up to 200µg/mL (whereuncaria rhynchophylla is thought to mediate the serotonin like effects) there was no influence on 5-HT2B receptors nor the serotonin transporter.[6]

 

And what about mixing it with:

 

-Ziziphus jujuba

 

Jujube flavonoids have once been found to act synergistically with 2mg/kg 5-HTP in inducing sleep in rats.

 

 

these results suggested that the hypnotic effect of jujubosides on normal rats may be influenced by circadian rhythm and the serotonergic system may involve in the hypnotic effect of jujubosides. Jujubosides may be good source of lead compounds for novel hypnotics.

 

and:

 

-Albizia julibrissin

 

The present study was undertaken to investigate the antidepressant-like effects of the methylene chloride fraction of Albizzia julibrissin (MCAJ) using a tail suspension test in mice. MCAJ was orally administered at 50, 100, or 200 mg/kg to mice, 1 h before the tail suspension test. Acute treatment with MCAJ at 200 mg/kg significantly reduced the immobility time compared with the control group, and thus showed an antidepressant-like effect. This effect was comparable to that of imipramine at 10 mg/kg. This antidepressant-like effect was reversed by treatment with WAY-100635 (a 5-HT1A receptor antagonist) or pindolol (a 5-HT1A/1B receptor antagonist). However, the antidepressant effect of MCAJ was not effected by treatment with GR55562 (a 5-HT1B receptor antagonist) or ketanserin (a 5-HT2A receptor antagonist). Therefore, our findings suggest that MCAJ exerts its antidepressant-like effect via the 5-HT1A receptor system.

Edited by William Sterog, 23 June 2015 - 12:45 PM.

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#76 Flex

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Posted 23 June 2015 - 11:32 PM

 

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..

 

Wait, is Sodium Butyrate a 5-HT1A agonist or antagonist? Or inverse/partial? Please clarify. I can't seem to find much on this. 

Interestingly, though... Check this article:

Butyric Acid: an Ancient Controller of Metabolism, Inflammation and Stress Resistance?

 

 

Couldnt find on a quick search anything about any 5-ht1a interaction.

Got also too many results mentioning GABA instead of Butyric Acid
 



#77 Flex

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Posted 29 June 2015 - 01:06 AM

Found this, for what it's worth:

 

Involvement of norepinephrine and serotonin system in antidepressant-like effects of hederagenin in the rat model of unpredictable chronic mild stress-induced depression.

HG showed that significant increases of norepinephrine and serotonin levels and exhibited a tendency to increase the expression of 5-hydroxytryptamine (serotonin) 1A receptor mRNA, and to significantly decrease the expression of the mRNA for the serotonin transporter (5-HTT). However, there were no significant differences in the expression of the brain-derived neurotrophic factor.

http://www.ncbi.nlm....pubmed/25471378

 

The decrease of the 5-htt should, from my laymans view, be actually contraindicative for PSSD.

Though I cant say it for sure.


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#78 gamesguru

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Posted 11 September 2015 - 01:47 AM

Found these:

A novel ergot alkaloid as a 5-HT(1A) antagonist
In the course of a search for small-molecule inhibitors of 5-hydroxytryptamine receptors we have identified a novel ergoline derivative (1) from the fungal culture of Dicyma sp. This compound has a pK(i) of 10.2 versus the 5-HT1A receptor subtype. The structure was elucidated by extensive NMR spectroscopy and mass spectrometry.

----------

AGONISTS:
Geissoschizine methyl ether, an alkaloid in Uncaria hook, is a potent serotonin 1A receptor agonist and candidate for amelioration of aggressiveness and sociality by yokukansan

Yokukansan (YKS), a traditional Japanese medicine, is composed of seven kinds of dried herbs. It is widely prescribed in clinical situation for treating psychiatric disorders such as aggressiveness in patients with dementia. We previously demonstrated that YKS and Uncaria hook (UH), which is a constituent herb of YKS, had a partial agonistic effect to 5-HT1A receptors in vitro... ameliorated the isolation-induced increased aggressiveness and decreased sociality, and these ameliorative effects were counteracted by coadministration of 5-HT1A receptor antagonist WAY-100635, or disappeared by eliminating UH from YKS.

 

Tetrahydroberberine, an isoquinoline alkaloid isolated from corydalis tuber, enhances gastrointestinal motor function.

a significantly higher shift in the pressure-volume curve by THB (10 μg/kg, p < 0.05), which was inhibited by (WAY-100635), a 5-HT1A antagonist

 

CBD was already mentioned first page, just posting a different study

Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors

Seven days after predator exposure 5-HT1A mRNA expression was up regulated in the frontal cortex and hippocampus. CBD and paroxetine failed to prevent this effect. No change in BDNF expression was found. In conclusion, predator exposure promotes long-lasting up-regulation of 5-HT1A receptor gene expression in the hippocampus and frontal cortex. Repeated CBD administration prevents the long-lasting anxiogenic effects observed after predator exposure probably by facilitating 5-HT1A receptors neurotransmission. Our results suggest that CBD has beneficial potential for PTSD treatment and that 5-HT1A receptors could be a therapeutic target in this disorder.


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#79 Area-1255

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Posted 11 September 2015 - 02:06 AM

Wonderful contribution my friend!

 

Found these:

A novel ergot alkaloid as a 5-HT(1A) antagonist
In the course of a search for small-molecule inhibitors of 5-hydroxytryptamine receptors we have identified a novel ergoline derivative (1) from the fungal culture of Dicyma sp. This compound has a pK(i) of 10.2 versus the 5-HT1A receptor subtype. The structure was elucidated by extensive NMR spectroscopy and mass spectrometry.

----------

AGONISTS:
Geissoschizine methyl ether, an alkaloid in Uncaria hook, is a potent serotonin 1A receptor agonist and candidate for amelioration of aggressiveness and sociality by yokukansan

Yokukansan (YKS), a traditional Japanese medicine, is composed of seven kinds of dried herbs. It is widely prescribed in clinical situation for treating psychiatric disorders such as aggressiveness in patients with dementia. We previously demonstrated that YKS and Uncaria hook (UH), which is a constituent herb of YKS, had a partial agonistic effect to 5-HT1A receptors in vitro... ameliorated the isolation-induced increased aggressiveness and decreased sociality, and these ameliorative effects were counteracted by coadministration of 5-HT1A receptor antagonist WAY-100635, or disappeared by eliminating UH from YKS.

 

Tetrahydroberberine, an isoquinoline alkaloid isolated from corydalis tuber, enhances gastrointestinal motor function.

a significantly higher shift in the pressure-volume curve by THB (10 μg/kg, p < 0.05), which was inhibited by (WAY-100635), a 5-HT1A antagonist

 

CBD was already mentioned first page, just posting a different study

Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors

Seven days after predator exposure 5-HT1A mRNA expression was up regulated in the frontal cortex and hippocampus. CBD and paroxetine failed to prevent this effect. No change in BDNF expression was found. In conclusion, predator exposure promotes long-lasting up-regulation of 5-HT1A receptor gene expression in the hippocampus and frontal cortex. Repeated CBD administration prevents the long-lasting anxiogenic effects observed after predator exposure probably by facilitating 5-HT1A receptors neurotransmission. Our results suggest that CBD has beneficial potential for PTSD treatment and that 5-HT1A receptors could be a therapeutic target in this disorder.

 

 


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#80 Flex

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Posted 30 January 2016 - 08:05 PM

I had recently some success with Coriander spice. Cant tell which part, it was just the normal powder from the shelf.

After ingestion of normal and higher ammounts (ca.0.8 gram), I felt a boost in sexuality. It lasted ca. 3 hours IIRC.

 

The downside was a feeling of unconfortableness / a slight pressure in the head at the higer dose.

I dont know what other side-effects and interactions might occur at higher doses, so take care.



#81 sativa

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Posted 31 January 2016 - 11:26 AM

Regarding zinc:

Activity at DAT. Potential for Zn to act as a DRI "as long as the cell meets the right conditions"?

Zinc regulates the dopamine transporter in a membrane potential and chloride dependent manner.

http://www.ncbi.nlm....pubmed/19000913

Also Zn "enhances the "efflux" of dopamine, meaning the rate at which dopamine is dumped into the synapse by any means [in this case it is probably by firing the neuron]."

Zinc Potentiates an Uncoupled Anion Conductance Associated With the Dopamine Transporter.


The binding of zinc to endogenous DAT residues exhibits a noncompetitive inhibition of DA (Norregaard et al. 1998) and MPP+ (Scholze et al. 2002) transport but not substrate binding, suggesting conformational changes in ECLs 2 and 4 are necessary for substrate translocation. In addition to inhibiting substrate uptake, the binding of zinc to DAT promotes the reverse transport of substrate (Scholze et al. 2002; Meinild et al. 2004). Zinc immobilization of ECLs 2 and 4 potentiates a DAT-mediated, uncoupled chloride conductance that modulates the cellular membrane potential, and as a consequence, elicits a simultaneous allosteric inhibition of uptake and enhancement of efflux (Meinild et al. 2004).

https://www.research...9_49_671-49_679


So, Zinc "doesn't just inhibit the transporter when the membrane potential is in the firing phase. It alters the membrane potential so that the transporter is continuously shut down. It also reverses the transporter" (amphetamine also reverses the dopamine transporter)

Regarding 5-HT1A:

Limonene is a potential agonist of 5-HT1A. This is just a study I found from a quick Google search. Lemon essential oil is definitely psychoactive in me.

Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT1A-receptors and reduces cholesterol after repeated oral treatment

http://bmccomplement...1472-6882-13-42


Edited by sativa, 31 January 2016 - 11:29 AM.

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#82 normalizing

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Posted 31 January 2016 - 07:51 PM

which type of zinc tho? there are so many supplemental forms but naturally zinc is bound to proteins in food, so its not clear which variant can work best and how much is the absorption anyway



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#83 voyteck

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Posted 05 July 2018 - 06:57 PM

Dear all,

 

I am looking for cure for my buspirone-induced PSSD.

I stopped it 10 weeks ago after hellish withdrawal.

I already read some topics - including this - but I don't have enough knowledge and mental power (brainfog from depression etc.) to decide which thing to try. Berberine or ginkgo? Or maybe something different.

I don't want to make things worse (primum non nocere). I don't have libido but can still get erection and ejaculation (premature) when forced with porn.

 

Please help!

If anyone's interested I'll give more details.

 



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#84 DaveX

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Posted 23 January 2020 - 04:34 PM

Would 5-HTP, as a readily-available serotonin-precursor, act as a postsynaptic 5HT1a agonist? Probably presynpatic as well, but presynaptic modulators are known, whereas it seems there are only postsynaptic antagonists among natural substances, but not agonists, whereas, though mostly with some ambiguity, is is suggested the antagonism itself is the good thing, rather than the following upregulation, which would be a bad thing. Making agonists preferable, though rare. (Or maybe that's just me, but what follows after antagonism feels like sh*t, while antagonism itself doesn't.)

 

I have only found Astragalus extract as a possible postsynaptic 5HT1a agonist, although it is not mentioned that it is "postsynaptic", and I have only inferred that from the test substances that were used. Although it is not easy to find clear information even on them sometimes, or some of them are mixed too. I will post a random study of this effect, I believe you will find it is a postsynaptic agonist after checking the profile of the other drug: 

https://www.ncbi.nlm...pubmed/24709311

 

Regardless, postsynaptic agonists are lacking, I suppose 5-HTP is  a good bet.

 

 

In addition: maybe Bacopa:

https://www.newhope....otonin-receptor

" The study concluded that the Bacopa extract displaces antagonist [3H]Ketanserin from serotonin receptor 5HT2a isolated from rats, and exhibited even stronger effects in its displacement of agonist 8-OH-DPAT from the 5HT1a receptor.

The study also concluded that the Bacopa extract decreases cAMP production in cells with 5HT1a receptors, suggesting it causes an agonistic effect. "

 

Both 8-OH-DPAT and WAY-100635, mentioned in the other study, seem to be postsynaptic, although one is an agonist and the other an antagonist. Even so, it seems confusing that they are both postsynaptic, since one would expect presynaptic action to be at least equally common, and one of them possibly does both. (And some effects are in fact explained by action on one side influencing the action on another side.) In this way it can be hard to be sure what something does.


Edited by DaveX, 23 January 2020 - 05:33 PM.






Also tagged with one or more of these keywords: ginkgo biloba, berberine, natural 5-ht1a, agonists, antagonists, 5ht1a antagonist, natural herbal, natural serotonin, blocker, pssd

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