Why do some drugs such as Trazodone/Gabapentin calm or put you to sleep at lower doses yet have opposite effects at higher doses?

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Why do some drugs such as Trazodone/Gabapentin calm or put you to sleep at lower doses yet have opposite effects at higher doses?

In: Chemistry
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Edit: I thought I was in the r/askscience sub lmfao sorry

I am not a scientist but I have wondered the same thing before so I did a little research. Take anything I say with a grain of salt; just trying my hand at this.

> Although its mechanism of action is not fully understood, the main pharmacological action of trazodone is blockade of the serotonin 5-HT2A receptor (1mg of trazodone roughly blocked half of brain 5-HT2A receptors). Increasing trazodone dose (50mg) causes antagonism on histamine H1 and α1-adrenergic receptors. The blocking of the 5-HT2A, histamine H1, and alpha receptors is thought to produce the hypnotic effect reported for low doses of trazodone (25–100mg).11 At these low doses, trazodone induces and maintains sleep without causing daytime drowsiness or tolerance, mainly because of its short half-life (3–6 hours).

[Source](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842888/)

I found this info on trazadone but haven’t looked into the other substances you mentioned yet. So what I took away from this is that while the exact mechanism of action of trazadone is still unknown, we DO know that only as little as 1mg of it can produce the hypnotic effects that combat insomnia. Also, at higher doses trazadone will act as an antagonist to the histamine H1 and a1 adrenic receptors. This is where it goes over my head but I think that the interference of one or both of these receptors could produce an effect on your body that makes the hypnotic effect less viable. I believe agonism of the histamine receptor causes hypotension so the antagonist response could be hypertension which in turn would make it harder to fall asleep. I have no idea what antagonism of the adrenic receptor would constitute.

Another substance that works better at lower doses is Melatonin btw. I hope someone more qualified than myself comes along to answer your questions! 🙂