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Misc Cyproheptadine is an antagonist of serotonin? How sure are you about that?

The Holy Quadruplty

The Holy Quadruplty

Bluelighter
Joined
Feb 9, 2022
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Cyproheptadine apparently blocks serotonin even though I'm 99% sure that antihistamines just block the reuptake of serotonin which increases serotonin. It says that Cyproheptadine can be used to block the serotonergic effects of other drugs since it's an antagonist of serotonin they say atleast. Is that true for just Cyproheptadine, or is it really just a serotonin reuptake inhibitor?
For example another antihistamine "Chlorpheniramine" has SSRI effects, and increases serotonin. It doesn't block serotonin so is it just different with Cyproheptadine? I've never even tried it. It's one of the only drugs I haven't tried.
 
The Holy Quadruplty said:
Cyproheptadine apparently blocks serotonin even though I'm 99% sure that antihistamines just block the reuptake of serotonin which increases serotonin. It says that Cyproheptadine can be used to block the serotonergic effects of other drugs since it's an antagonist of serotonin they say atleast. Is that true for just Cyproheptadine, or is it really just a serotonin reuptake inhibitor?
For example another antihistamine "Chlorpheniramine" has SSRI effects, and increases serotonin. It doesn't block serotonin so is it just different with Cyproheptadine? I've never even tried it. It's one of the only drugs I haven't tried.
Click to expand...

Cyproheptadine has negligible affinity for the SERT (serotonin transporter) and as such can't be thought of a serotonin reuptake inhibitor (at least in any clinically relevant sense):



So in answer to the two questions in the title of this thread 1) yes and 2) I'm pretty sure about it 🤔🤣.
 
negrogesic said:
Cyproheptadine has negligible affinity for the SERT (serotonin transporter) and as such can't be thought of a serotonin reuptake inhibitor (at least in any clinically relevant sense):



So in answer to the two questions in the title of this thread 1) yes and 2) I'm pretty sure about it 🤔🤣.
Click to expand...
Yes it blocks serotonin, and not a re uptake inhibitor of it?
 
The Holy Quadruplty said:
Yes it blocks serotonin, and not a re uptake inhibitor of it?
Click to expand...

Direct binding to a specific 5HT receptor site is post-synaptic whereas the transport blockade occurs on the other side of the synaptic cleft (ie, pre-synaptic).



So in the case of cyproheptadine, it binds directly to various post-synaptic serotonin receptor sites (especially 5HT2x). It has negligible interaction with the transporter (ie, SERT).
 
I think cyproheptadine is the standard antidote against serotonin syndrome so it must work and this includes not being a SSRI.
 
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