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Do anihistamines bind to opioid receptors?

The Holy Quadruplty

The Holy Quadruplty

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Feb 9, 2022
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We know promethazine and other antihistamines bind to sigma opioid receptors. I was looking at the binding affinities for promethazine on the target predictor and it says it may bind to mu, delta, and kappa opioid receptors. I looked up chlorpheniramine and the same thing came up! I was wondering if anyone had any information on this, and if they would be agonist or antagonist of the receptors if so?
 
Doubtful.

Even if they did, it would probably be completely negligible.

If you can find any studies showing naloxone reverses their effects, then you'd have your answer, but if there aren't any, then it's most likely cause they don't bind to mu.
 
DeathIndustrial88 said:
Doubtful.

Even if they did, it would probably be completely negligible.

If you can find any studies showing naloxone reverses their effects, then you'd have your answer, but if there aren't any, then it's most likely cause they don't bind to mu.
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I feel that they might even though I hope they don't honestly cuz I take both Promethazine and chlorpheniramine with my Subutex. That's why I was wondering if they'd be antagonist at all even though I highly doubt they do bind to opioid receptors, and if so not very strongly.
 
Update I just read that chlorpheniramine potentiated morphine antinoceceptive effects, and that chlorpheniramine antinoceceptive effect is likely from the opioid system. It was a study on chlorpheniramine, rantadine, and morphine. It said naloxone and rantadine blocked morphines noceceptive effects, but chlorpheniramine potentiated it. That doesn't tell us if it binds to mu or kappa receptors though.
 
The Holy Quadruplty said:
We know promethazine and other antihistamines bind to sigma opioid receptors. I was looking at the binding affinities for promethazine on the target predictor and it says it may bind to mu, delta, and kappa opioid receptors. I looked up chlorpheniramine and the same thing came up! I was wondering if anyone had any information on this, and if they would be agonist or antagonist of the receptors if so?
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No. They bind to histaminergic receptors. If they bound to opioid receptors, they would decrease the effects of opioids, rather than potentiate them.
 
They would have to be antagonists to decrease the effects of an opioid.

Or have high binding affinity with very low intrinsic activity.

Otherwise, it would just be stacking another opioid ontop of another one.



Doesn't promethazine have antipsychotic effects too? As in, it decreases dopamine?

I don't doubt that you get potentiation and decent effects, just confused how it would work if promethazine decreases dopamine release.

I've only had prometh once, with codeine and it just put me to sleep (no euphoria, no warm fuzzies). Also made my head feel a little dulled and spacey.
But there must be something there for it to be a popular thing with people. It just didn't appeal to me much. But then again I haven't had a chance to try it since.
 
The Holy Quadruplty said:
How would they decrease the effects because I definitely feel the potentiation!
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That's my point. Anti-histamines potentiate opioids, but IF they DID bind to opioid receptors, they would be taking up space that the opioid would normally fill and so would decreased the effects of opioids were that the case.
 
DeathIndustrial88 said:
They would have to be antagonists to decrease the effects of an opioid.

Or have high binding affinity with very low intrinsic activity.

Otherwise, it would just be stacking another opioid ontop of another one.



Doesn't promethazine have antipsychotic effects too? As in, it decreases dopamine?

I don't doubt that you get potentiation and decent effects, just confused how it would work if promethazine decreases dopamine release.

I've only had prometh once, with codeine and it just put me to sleep (no euphoria, no warm fuzzies). Also made my head feel a little dulled and spacey.
But there must be something there for it to be a popular thing with people. It just didn't appeal to me much. But then again I haven't had a chance to try it since.
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Promethazine and all other antipsychotics are known to be dopamine antagonist which is true, but they actually just block it's re-up take and the other nerutransmitters besides histamine increasing dopamine! I can say from experience too!
 
ChemicallyEnhanced said:
That's my point. Anti-histamines potentiate opioids, but IF they DID bind to opioid receptors, they would be taking up space that the opioid would normally fill and so would decreased the effects of opioids were that the case.
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Not if they're agonist tho. I'd rather them not bind to them actually tho unless it doesn't negatively effect my Subutex at all.
 
DeathIndustrial88 said:
They would have to be antagonists to decrease the effects of an opioid.

Or have high binding affinity with very low intrinsic activity.

Otherwise, it would just be stacking another opioid ontop of another one.



Doesn't promethazine have antipsychotic effects too? As in, it decreases dopamine?

I don't doubt that you get potentiation and decent effects, just confused how it would work if promethazine decreases dopamine release.

I've only had prometh once, with codeine and it just put me to sleep (no euphoria, no warm fuzzies). Also made my head feel a little dulled and spacey.
But there must be something there for it to be a popular thing with people. It just didn't appeal to me much. But then again I haven't had a chance to try it since.
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Yea I doubt they have anything OTC that binds to opioid receptors in anyway any more stronger than Buprenorphine does. Promethazine definitely potentiates my Subutex and Xanax with some chlorpheniramine and weed thrown in too. Especially smoking a lot of weed seems to really enhance it! It's weird though that promethazine and chlorpheniramine we're the only antihistamines I saw that possibly bind to the opioid receptors. Doxylamine, Diphenhydramine, Seroquel, and Zyrtec didn't. I'm going to look up more when I get the chance!
 
The Holy Quadruplty said:
Yea I doubt they have anything OTC that binds to opioid receptors in anyway any more stronger than Buprenorphine does. Promethazine definitely potentiates my Subutex and Xanax with some chlorpheniramine and weed thrown in too. Especially smoking a lot of weed seems to really enhance it! It's weird though that promethazine and chlorpheniramine we're the only antihistamines I saw that possibly bind to the opioid receptors. Doxylamine, Diphenhydramine, Seroquel, and Zyrtec didn't. I'm going to look up more when I get the chance!
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Interesting! Let me know what else you find.

Yeah, Loperamide is OTC and I'd say it's probably the closest thing to an OTC opioid we have in the US. But it sucks & is dangerous. It's a full agonist but gets pumped back out of the brain pretty quickly.

I've had a bottle of chlorpheniramine malaete for a long time now but I've read some gruesome things about what high doses can do to your body, so I've avoided it for all this time.

I some times use benadryl when I'm nauseous and if my tolerance to it is nil, the benadryl will add it's own kind of 'comforting blanket' which boosts the experience.
But if I try to use benadryl again the next day or even the day after, it doesn't do much.
 
I believe that they compete for metabolism (opioid sparing) and they impart SOME of the actions of opioids.
 
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