Misc chlorpheniramine 5ht2a binding affinities

[The Holy Quadruplty]

Chlorpheniramine 5ht2a binding affinities of rats is like 3 thousand something. How much would that be for a human? I know it binds to serotonin very strongly, but would like to know how strongly to that specific receptor.

 

[negrogesic]

Chlorpheniramine 5ht2a binding affinities of rats is like 3 thousand something. How much would that be for a human? I know it binds to serotonin very strongly, but would like to know how strongly to that specific receptor.

It sounds like you might be reading it backwards. The higher the Ki value (or IC50, EC50 etc) the lower the affinity. So a ligand with a Ki value of 3000nM has lower affinity than one with a Ki value of 3nM.

Also keep in mind that sometimes affinities are expressed in different scales as necessary, for instance 3000nM = 3uM (nanomolar to micromolar).

 

[The Holy Quadruplty]

It sounds like you might be reading it backwards.

No I'm not I already knew that, but it has a 15 nanomolar for the serotonin receptor it says. So I know it has strong serotonergic effects, and I've read it multiple times. I'm just trying to figure how strong it binds to that receptor the 5ht2a. You can see the binding affinities for it on Wikipedia.

 

[negrogesic]

No I'm not I already knew that, but it has a 15 nanomolar for the serotonin receptor it says. So I know it has strong serotonergic effects, and I've read it multiple times. I'm just trying to figure how strong it binds to that receptor the 5ht2a. You can see the binding affinities for it on Wikipedia.

Yeah, for the serotonin transporter it has high affinity (ie, the ~15nm) but as the 3000nM @ 5HT2A figure suggests, it has very low affinity for the post-synaptic 5HT sites. The fact that the data is presented for rat versus human doesn't matter much in this case; chlorpheniramine doesn't really bind to the post-synaptic 5HT receptor sites in any clinically significant way, but it does potently block reuptake due to a high affinity for the transporter. But this gives it very different effects than a 5HT2A agonist.

 

[The Holy Quadruplty]

Yeah, for the serotonin transporter it has high affinity (ie, the ~15nm) but as the 3000nM @ 5HT2A figure suggests, it has very low affinity for the post-synaptic 5HT sites. The fact that the data is presented for rat versus human doesn't matter much in this case; chlorpheniramine doesn't really bind to the post-synaptic 5HT receptor sites in any clinically significant way, but it does potently block reuptake due to a high affinity for the transporter. But this gives it very different effects than a 5HT2A agonist.

But it still increases Serotonin in general pretty strongly right?

 

[d1nach]

I think this would make it more like an SSRI like prozac so it might block the reuptake of serotonin technically increasing serotonin But not in a way I think your looking for directly via 5ht1 and 5ht2 receptors like mdma and lsd.

Perhaps a different receptor is causing the effects you are associating with serotonin.

Or

Maybe (while not recommended) if your taking this like daily and at a certain dose maybe over many weeks your mood is being boosted via sert inhibition like a very weak mdma or lsd by indirectly causing long term changes from the serotonin interacting with the 5ht receptors .

But, if this is the case I'd recommend prozac or any SSRI (if you can afford it I know medical access is a nightmare)

But I think most likely a different receptor.

Hope I don't come across as rude. Not trying to discredit your experience just maybe the reason for your experience might be elsewhere

 

[The Holy Quadruplty]

I think this would make it more like an SSRI like prozac so it might block the reuptake of serotonin technically increasing serotonin But not in a way I think your looking for directly via 5ht1 and 5ht2 receptors like mdma and lsd.

Perhaps a different receptor is causing the effects you are associating with serotonin.

Or

Maybe (while not recommended) if your taking this like daily and at a certain dose maybe over many weeks your mood is being boosted via sert inhibition like a very weak mdma or lsd by indirectly causing long term changes from the serotonin interacting with the 5ht receptors .

But, if this is the case I'd recommend prozac or any SSRI (if you can afford it I know medical access is a nightmare)

But I think most likely a different receptor.

Hope I don't come across as rude. Not trying to discredit your experience just maybe the reason for your experience might be elsewhere

Interestingly Diphenhydramine is like the opposite the affinity for the serotonin transporter is like 3,000 something I think for humans (ki values), but it's like 260 I'm pretty sure for the 5ht2a so would that make it more like drugs such as LSD? I also understand you're just trying to help, and not trying to be rude! You're good no worries!

 

[d1nach]

Can you find anything about it being an agonist

This is the best I could find suggesting maybe it's an antagonist dph

Analgesic Effects of 1st Generation Anti-histamines in Mice

Access full-text academic articles: J-STAGE is an online platform for Japanese academic journals.

www.jstage.jst.go.jp

 

[The Holy Quadruplty]

Can you find anything about it being an agonist

This is the best I could find suggesting maybe it's an antagonist dph

Analgesic Effects of 1st Generation Anti-histamines in Mice

Access full-text academic articles: J-STAGE is an online platform for Japanese academic journals.

www.jstage.jst.go.jp

When they say antagonist of the serotonin receptors I'm pretty sure they mean they block the re-up take of serotonin which increases it. I have read a lot about the increased serotonergic effects of antihistamines being good for anxiety, and other things like that. If I'm wrong please somebody let me know. They even say Chlorpheniramine could of been the first SSRI. I've also read it increases serotonin, and same with Diphenhydramine!

Just found this..

Diphenhydramine, a first-generation antihistamine that acts as an inverse agonist on the H1 receptor [3] may also inhibit the reuptake of serotonin. It is known that SSRIs like Fluoxetine are analogs of diphenhydramine [4]. Although weaker, diphenhydramine does retain some

Also just found this...

As a serotonin antagonist, hydroxyzine boosts the levels of serotonin in your brain by blocking it from being reabsorbed into the nerves in your brain (called neurons).

AKA when they were saying antagonist they really meant that they block the re-up take of serotonin which increases it. There's an antihistamine called Cyproheptadine that actually does block serotonin if I'm not mistaken, or atleast to some degree, but I'm not one hundred percent sure so make sure you do your research before trying to use it as a serotonin blocker. I'm also saying that I don't know forsure, because I don't want to say the wrong thing, and/or give false information! All the information I post it based on what I read, and I don't know much about chemistry so always do your own research!

 

[d1nach]

Ahh I think after rereading and getting distracted a few times I think issue is in translation

5ht are serotonin receptors I think it's a abbreviation for the chemical name of serotonin

Blocking the reuptake of serotonin increases the amount of serotonin

But 5ht receptors I think kinda like the type of locks serotonin can then act as a key for.

Then you could have different kinds of keys one that activates it or one that fits in but blocks it

The reason I think all of this matters is it seems like chlorpheniramine has high binding to the sert transporter not the 5ht2 receptors

And dph doesnt seem to have very strong inhibition at the sert transporter but a possible binding to the 5ht2a but could even an antagonist or not significant at a typical dose and I can't find much about it

So if your experiencing serotonin like effects immediately they typically activate the serotonin receptors 5ht1 and 5ht2

And blocking reuptake of the sert does BUT typically takes weeks

But what dph and chlor do have in common is h1 antag and mACh antag

Which h1 antag can make you feel calmer
Which is why I think it might me this

But mACh could (not proven safe don't recommend) alter bdnf causing a hypothetical rapid antidepressant effects but with risk of serious side effects or indirectly increasing dopamine (weakly compared other drugs)

I think I had too much coffee lol

 

[The Holy Quadruplty]

Ahh I think after rereading and getting distracted a few times I think issue is in translation

5ht are serotonin receptors I think it's a abbreviation for the chemical name of serotonin

Blocking the reuptake of serotonin increases the amount of serotonin

But 5ht receptors I think kinda like the type of locks serotonin can then act as a key for.

Then you could have different kinds of keys one that activates it or one that fits in but blocks it

The reason I think all of this matters is it seems like chlorpheniramine has high binding to the sert transporter not the 5ht2 receptors

And dph doesnt seem to have very strong inhibition at the sert transporter but a possible binding to the 5ht2a but could even an antagonist or not significant at a typical dose and I can't find much about it

So if your experiencing serotonin like effects immediately they typically activate the serotonin receptors 5ht1 and 5ht2

And blocking reuptake of the sert does BUT typically takes weeks

But what dph and chlor do have in common is h1 antag and mACh antag

Which h1 antag can make you feel calmer
Which is why I think it might me this

But mACh could (not proven safe don't recommend) alter bdnf causing a hypothetical rapid antidepressant effects but with risk of serious side effects or indirectly increasing dopamine (weakly compared other drugs)

I think I had too much coffee lol

What's bdnf?

 

[d1nach]

Nerve growth factor basically I think it's an alternative idea of how drugs with different mechanisms can cause antidepressant effects.

However, the evidence for ssris and ketamine is much higher than mACh antagonism. Especially the tolerability and human dosage.