5-HT1A Receptor Agonists May Treat Malaria

[Luann]

I wonder if OP saw the study that showed "being single" is linked to 5ht1a.

*Is not sure whether real science is involved or not*

 

[haidut]

I wonder if OP saw the study that showed "being single" is linked to 5ht1a.

*Is not sure whether real science is involved or not*

I was not aware of this study, so thanks for posting. It seems like higher serotonin, which is associated with higher 5-HT1A expression is associated with aversion to relationships.
"...Love-related behaviors, such as pair bonding and affective affiliation, are shown to be associated with the serotonin levels in the brain4–9. In non-human animals, decreasing serotonin levels via 5-HT1A receptor agonists diminishes female sexual receptivity and induces aggression towards male mates6,8. The G allele of the C-1019G (rs6295) polymorphism, which leads to higher expression of 5-HT1A gene, is related to decreased comfort with close relationships 9 . Thus it is possible that this 5-HT1A gene polymorphism is related to the likelihood of a young adult being in a relationship. This possibility was tested on 579 Chinese undergraduate students."

 

[Frankdee20]

I was not aware of this study, so thanks for posting. It seems like higher serotonin, which is associated with higher 5-HT1A expression is associated with aversion to relationships.
"...Love-related behaviors, such as pair bonding and affective affiliation, are shown to be associated with the serotonin levels in the brain4–9. In non-human animals, decreasing serotonin levels via 5-HT1A receptor agonists diminishes female sexual receptivity and induces aggression towards male mates6,8. The G allele of the C-1019G (rs6295) polymorphism, which leads to higher expression of 5-HT1A gene, is related to decreased comfort with close relationships 9 . Thus it is possible that this 5-HT1A gene polymorphism is related to the likelihood of a young adult being in a relationship. This possibility was tested on 579 Chinese undergraduate students."

Are we talking post or pre synaptic 5ht1a agonists ? Don’t these agonists do different things depending on which side ?

 

[dand]

@ haidut Interesting. I was just looking up what the mechanism for CBD's therapeutic effects are and evidently it is a pretty potent agonist of 5-HT1. I was confused because I thought that it in fact felt pretty dopaminergic. My muscles feel strong and I have great body control when I have taken CBD. Perhaps that agonism of 5-ht1 is actually dopaminergic is the reason?

 

[haidut]

@ haidut Interesting. I was just looking up what the mechanism for CBD's therapeutic effects are and evidently it is a pretty potent agonist of 5-HT1. I was confused because I thought that it in fact felt pretty dopaminergic. My muscles feel strong and I have great body control when I have taken CBD. Perhaps that agonism of 5-ht1 is actually dopaminergic is the reason?

I think the 5-HT1 receptor is the negative feedback mechanism on serotonin synthesis. I think it depends on the subreceptor agonism antagonism. 5-HT1A agonists and 5-HT1D antagonists lower serotonin synthesis and increase dopamine. So, depending on which sub-receptor CBD acts on it could increase dopamine.

 

[dand]

I think the 5-HT1 receptor is the negative feedback mechanism on serotonin synthesis. I think it depends on the subreceptor agonism antagonism. 5-HT1A agonists and 5-HT1D antagonists lower serotonin synthesis and increase dopamine. So, depending on which sub-receptor CBD acts on it could increase dopamine.

Appears to be an agonist :). Please see below.. Although, I did have some mildly serotogenic symptoms in my bowel movement after ingesting a large dose of CBD so it is likely a mixed bag. I don't understand how the receptor theory is both discredited in the Peat world, but we also use it as a guide in certain context :/ ? We have to never stop learning I suppose :).

https://www.ncbi.nlm.nih.gov/pubmed/16258853

 

[Andman]

https://www.selfhacked.com/blog/rs6295-the-single-and-self-transcendent-gene-5-ht1a-receptor/

maybe helpful?

 

[dand]

https://www.selfhacked.com/blog/rs6295-the-single-and-self-transcendent-gene-5-ht1a-receptor/

maybe helpful?

No, I did not find that to have any kind of cohesive/conceptual framework. It seemed vv reductive. Thank you for trying though.

 

[lvysaur]

I think Peatarian.com closed b/c it was overrun by people with serotonin-dominance. JK.

LOL

 

[haidut]

Appears to be an agonist :). Please see below.. Although, I did have some mildly serotogenic symptoms in my bowel movement after ingesting a large dose of CBD so it is likely a mixed bag. I don't understand how the receptor theory is both discredited in the Peat world, but we also use it as a guide in certain context :/ ? We have to never stop learning I suppose :).

Agonistic properties of cannabidiol at 5-HT1a receptors. - PubMed - NCBI

The receptors are there but whether the cell will let a chemical inside and how that chemical will react with the receptor depends on cellular energy reserves, water structure, and fat composition. As Peat said, some chemicals known to be agonists on a certain receptor can act as antagonists on the same receptor when the cell is low on ATP or thyroid, or has taken up too much water and is preparing to divide.

 

[dand]

The receptors are there but whether the cell will let a chemical inside and how that chemical will react with the receptor depends on cellular energy reserves, water structure, and fat composition. As Peat said, some chemicals known to be agonists on a certain receptor can act as antagonists on the same receptor when the cell is low on ATP or thyroid, or has taken up too much water and is preparing to divide.

Makes sense :). Context is everything, yet again.

 

[DavidGardner]

The schizophrenia and bipolar drug quetiapine is an antagonist at all serotonin receptor sites except for 5-HT1A, where it is a partial agonist.

5-HT1A activation does induce secretion of cortisol, growth hormone, and prolactin. It also makes me very cloudy-headed based on my experiences with buspirone and trazodone.

Hormonal and temperature responses to flesinoxan in normal volunteers: an antagonist study. - PubMed - NCBI

 

[ddjd]

Peat said that "agonizing" certain receptors like 5-HT1 actually has a negative feedback mechanism on serotonin release so it leads to reduced synthesis of serotonin and increase in dopamine. The Wikipedia page sort of backs up this claim of Peat by saying agonizing the 5-HT1 receptor triggers dopamine release, hence the effects of agonists like lisuride and bromocriptine on Parkinson's and schizophrenia.
5-HT1A receptor - Wikipedia

So is the fact that metergoline antagonises 5ht1 a bad thing then?

 

[haidut]

So is the fact that metergoline antagonises 5ht1 a bad thing then?

It should have been if it resulted in lower dopamine and high prolactin, but in reality the exact opposite happens and this is why it is used for hyperprolactinemia in Europe.
I guess we don't fully know the exact mechanisms of action of many drugs or the full spectrum of serotonin receptors and their subunits. Maybe there are subnits of 5-HT1 beyound D, and metergoline acts on them in a way that results in lower serotonin/prolactin and higher dopamine.

 

[Mauritio]

Has anybody tried flibanserin ?

 

[Mito]

5-HT1A agonists and 5-HT1D antagonists lower serotonin synthesis and increase dopamine. So, depending on which sub-receptor CBD acts on it could increase dopamine.

“…Hill coefficients obtained suggest that CBD is an allosteric modulator of 5-HT1A receptors (Hill, 1910; Goutelle et al., 2008).”

Cannabidiol Acts at 5-HT1A Receptors in the Human Brain: Relevance for Treating Temporal Lobe Epilepsy

Experimental evidence indicates that cannabidiol (CBD) induces anxiolytic and antiepileptic effects through the activation of 5-HT1A receptors. These receptors are coupled to Gi/o proteins and induce inhibitory effects. At present, the interaction of CBD with 5-HT1A receptors in the human brain...

www.frontiersin.org

 

[Frankdee20]

It should have been if it resulted in lower dopamine and high prolactin, but in reality the exact opposite happens and this is why it is used for hyperprolactinemia in Europe.
I guess we don't fully know the exact mechanisms of action of many drugs or the full spectrum of serotonin receptors and their subunits. Maybe there are subnits of 5-HT1 beyound D, and metergoline acts on them in a way that results in lower serotonin/prolactin and higher dopamine.

For that particular receptor, agonists and antagonists can have such action on either the pre synaptic or post synaptic side….each side has different effects depending on weather a substance is blocking or activating them. This contributes to more of the confusion surrounding what common knowledge we have, and without specifying if it’s pre or post activity, it all seems paradoxical or counterintuitive at times

 

[aliml]

FDA Approves First Oral Selective 5HT1A Receptor Agonist for MDD

Following a long path to approval, gepirone hydrochloride extended-release tablets (Exxua) is the first FDA-approved medication with this novel mechanism of action for adults with MDD.

www.psychiatrictimes.com