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Why do I get RLS from Mirtazapin and Promethazine?

Posted by Skeletor on April 28, 2020, at 16:31:50

Why do I get RLS from Mirtazapine and higher doses of Promethazine?
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On 15mg of Mirtazapine I had RLS and some strange tickling feeling in my lower stomach. (I masturbated a lot to get rid of it.)

On 15mg of Promethazine I am fine, but anything higher than 25mg and I get RLS and that tickling feeling.

What is going on? Which mechanism is involved?

https://academic.oup.com/sleep/article/43/2/zsz223/5610750

https://www.reddit.com/r/depressionregimens/comments/g0ty01/striatal_histamine_mechanism_in_the_pathogenesis/?ref=share&ref_source=embed&utm_content=title&utm_medium=post_embed&utm_name=c0c781fa1bf84b94a76dd59c5616893d&utm_source=embedly&utm_term=g0ty01

"It simply seems like histamine might have a role in RLS. Could it be as simple as that blocking histamine H1 receptors is bad for RLS? Or is it due to some kind of indirect interaction histamine has with dopamine?"

It would seem that this antihistamine theory might be true at least to some degree, although there are so many theories on RLS that it is difficult to see through it. Especially when you have antihistamine properties and anti-Dopamine properties rolled into one drug.

But Mirtazapine doesn't seem to have anti-Dopamine properties, so leaves the antihistamine action as culprit of RLS....

Promethazine has some anti D2 action, but it is ridiculously weak: D2=250, 5HT2A=170, H1=1 [nM] from Gillman's website. I doubt that it will do much in that regard.


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