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Both are quite similar, and that is no surprise, given that Notrtiptyline is Amitriptyline's major metabolite.

When comparing both, we can ascertain the following: Amitriptyline has somewhat more SERT blocking going on, so might be slightly more "serotonergic" than Nortriptyline, although I am not quite sure if clinically relevant. Both are equally strong NRIs and 5HT2 antagonists. Amitriptyline is a stronger ALPHA1 blocker compared to Nortriptyline, so might cause more postural hypotension. Amitrptyline is a stronger antihistamine than Nortriptyline, so might cause more sedation and appetite. Amitriptyline is a stronger anticholinergic than Nortriptyline, so will probably cause more side effects. (Although stronger sedative and anticholinergic properties might be welcome, depending on the condition)

What I am interested in: Who's been on both and how did they compare? (not only theoretically, but practically)

binding affinities:


picture source: https://abload.de/img/nortgpk1f.png


Edited by Skeletor
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@mikl_pls you've taken at least nortriptyline before, yes? Have you taken both?

@Skeletor nortriptyline does seem to have more NRI effect and less sedative effect than amitriptyline. Nortriptyline is probably more like Fetzima (levomilnacipran) with high NET occupancy at all doses and greater SERT occupancy with higher dosing. Everything I've read about nortriptyline almost describes it as a tricyclic version of bupropion without the dopamine reuptake inhibition. However nortriptyline is a potent 5HT2C antagonist which would disinhibit the release of norepinephrine and dopamine and produce a similar effect. Nortriptyline has potential in the treatment of smoking cessation and ADHD as well.

On the flip-side, amitriptyline has more evidence for sleep-promoting effects. The combination blockade of muscarinic acetylcholine receptors, H1 histamine receptors, and alpha-1 adrenergic receptors at bedtime would be a very sedating pill.

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@Skeletor, I've tried both, and neither one helped with my depression.....I will say one thing, though..... Amitriptyline had more side effects than nortriptyline, at least for me it did......Amitriptyline made me feel so sedated throughout the day, even though I took it at night, and it also caused significant weight gain for me......Nortriptyline had very little side effects for me, but it did nothing for my depression, as I mentioned.

As I always say, everyone's different......I hope you have success with whatever you choose.

Edited by CrazyRedhead
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