What Is The Mechanism Behind Cyproheptadine's Sedation Effect?

[Brian]

I haven't been able to figure this one out through my own research. Does anybody know of any studies that explain it?

 

[jyb]

To be exact, it's not specific to cypro. Remeron feels very similar in effects, including the sedation side effect. But I would also be interested to know why.

 

[haidut]

All first generation antihistamines have this effect. In general, since histamine is presumed to be responsible for keeping us awake, blocking histamine would result in sedation/sleep. Also, histamine is an excitatory neurotransmitter in the brain an antagonizing it would lead to sedation. See this study.
http://www.ncbi.nlm.nih.gov/pubmed/8008209

Finally, drugs that are muscarinic antagonists are sedating due to their effects on dopamine. In general, pro-dopamine drugs like cyproheptadine would be sedating. This is confirmed by the sedating properties of drugs like lisuride, bromocriptine, cabergoline, etc.

 

[Koveras]

There is a relationship between histamine and the orexin/hypocretin system that promotes wakefulness.

Interactions of the orexin/hypocretin neurones and the histaminergic system.

 

[barefooter]

post 82207 In general, pro-dopamine drugs like cyproheptadine would be sedating. This is confirmed by the sedating properties of drugs like lisuride, bromocriptine, cabergoline, etc.

I thought I'd read on the forums before about cypro lowering dopamine. Am I mistaken, or can prolonged use of it actually lower dopamine?

 

[haidut]

post 118487

post 82207 In general, pro-dopamine drugs like cyproheptadine would be sedating. This is confirmed by the sedating properties of drugs like lisuride, bromocriptine, cabergoline, etc.

I thought I'd read on the forums before about cypro lowering dopamine. Am I mistaken, or can prolonged use of it actually lower dopamine?

It seems to depend on the person and the dose. In lower doses of 4mg daily cyproheptadine will probably not affect dopamine. I also know people who take 24mg daily and their prolactin went down.

 

[docall18]

I found that when i am on a lower dose of thyroid i get way more sedated from cypro than when i up my dose.

 

[mujuro]

Central H1 receptor antagonism.

EDIT - actually I just found this on the wiki page.

The expression of NF-κB, the transcription factor that regulates inflammatory processes, is promoted by the constitutive activity of the H1 receptor as well as by agonists that bind at the receptor.[3] H1-antihistamines have been shown to attenuate NF-κB expression and mitigate certain inflammatory processes in associated cells.[3]

Interesting. I'm sure haidut has probably already covered this in the main cypro thread.

 

[haidut]

post 118656 Central H1 receptor antagonism.

EDIT - actually I just found this on the wiki page.

The expression of NF-κB, the transcription factor that regulates inflammatory processes, is promoted by the constitutive activity of the H1 receptor as well as by agonists that bind at the receptor.[3] H1-antihistamines have been shown to attenuate NF-κB expression and mitigate certain inflammatory processes in associated cells.[3]

Interesting. I'm sure haidut has probably already covered this in the main cypro thread.

And in light of the finding that H1 antagonism lowers NF-kB, here are some recent news articles saying lowering NF-kB may be a viable treatment for the most common and deadliest brain cancer.
http://www.ndtv.com/health/new-target-f ... dy-1264106
http://medicalxpress.com/news/2016-01-s ... eadly.html

 

[mujuro]

Well that's another pro for my current medication protocol including the 2nd-gen atypical antipsychotic quetiapine which is a very potent H1 antagonist. As far as sedation goes, cyproheptadine is to quetiapine as a light drizzle is to a hailstorm. I know there is a relationship between NF-kB and CO, for example http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0008139 and http://bmcgastroenterol.biomedcentral.com/articles/10.1186/1471-230X-10-42.

 

[tomisonbottom]

Doesn't the sedation effect of Cypro wear off though after days, or weeks on it?

 

[Rafael Lao Wai]

Doesn't the sedation effect of Cypro wear off though after days, or weeks on it?

Yeah, it either wears off or the person gets used to it. I think in my case it's a combination of both: I got used to it but it's a milder sedation now.

 

[Mauritio]

There is a relationship between histamine and the orexin/hypocretin system that promotes wakefulness.

Interactions of the orexin/hypocretin neurones and the histaminergic system.

Caffeine also stimulates orexin , I hope that doenst mean it also stimulates histamine...

Stimulant doses of caffeine induce c-FOS activation in orexin/hypocretin-containing neurons in rat. - PubMed - NCBI


Also serotonin lowers orexin , but does that mean that orexin also lowers serotonin ?

 

[redsun]

Caffeine also stimulates orexin , I hope that doenst mean it also stimulates histamine...

Stimulant doses of caffeine induce c-FOS activation in orexin/hypocretin-containing neurons in rat. - PubMed - NCBI


Also serotonin lowers orexin , but does that mean that orexin also lowers serotonin ?

What's wrong with a little more histamine? Histamine is a very vital neurotransmitter. Caffeine increases glutamate which will activate histaminergic neurons and help promote wakefulness seeing as histamine has an important role in that. I also read of caffeine blocking DAO to some degree. Orexin also is needed for histamine.

Caffeine promotes glutamate and histamine release in the posterior hypothalamus

THE REGULATION OF SLEEP AND WAKEFULNESS BY THE HYPOTHALAMIC NEUROPEPTIDE OREXIN/HYPOCRETIN

 

[Mauritio]

You just assume it's just a little. And a little might be a little too much for someone who already has too much histamine. Also histamine raises estrogen and inflammation.

 

[redsun]

You just assume it's just a little. And a little might be a little too much for someone who already has too much histamine. Also histamine raises estrogen and inflammation.

Someone that already has too much histamine has no need for caffeine for its most common use which is to promote wakefulness and alertness.

 

[Mauritio]

Someone that already has too much histamine has no need for caffeine for its most common use which is to promote wakefulness and alertness.

The need might be there (liver benefits) but the practicality of it might be difficult that's right.

 

[NewACC]

It seems to depend on the person and the dose. In lower doses of 4mg daily cyproheptadine will probably not affect dopamine. I also know people who take 24mg daily and their prolactin went down.

Cypro's antidopaminergic effect is so strange. I feel heavy anticholinergic and antihistamine effect of cypro over first week, which are very unpleasant, but then It feels so prodopamine or at least antiinflammatory and antidepressant. And there are only few studies on Cypro's antidopaminergic properties and their's content is very abstract. if you look at books about antihistamines in general, then not a word will be said about the antidopaminergic activity of cypro. Unless research with rat receptors. It is so strange that such a weighty effect for the pharmacological context of such an old drug has not been investigated with cloned human receptors or with the help of radionuclides on living people.

 

[NewACC]

What's wrong with a little more histamine? Histamine is a very vital neurotransmitter. Caffeine increases glutamate which will activate histaminergic neurons and help promote wakefulness seeing as histamine has an important role in that. I also read of caffeine blocking DAO to some degree. Orexin also is needed for histamine.

Caffeine promotes glutamate and histamine release in the posterior hypothalamus

THE REGULATION OF SLEEP AND WAKEFULNESS BY THE HYPOTHALAMIC NEUROPEPTIDE OREXIN/HYPOCRETIN

In addition prohistamine action of fasting is maybe the maine reason of euphoric and arosual fasting effect

 

[NewACC]

Someone that already has too much histamine has no need for caffeine for its most common use which is to promote wakefulness and alertness.

A lot of us aren't using coffee as stimulator, just more like strong protective and antiinflammatory agent