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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 4 of 4. This is the beginning of the thread.
Posted by undopaminergic on October 9, 2020, at 8:42:33
Of all drugs classified as "antidepressants", trimipramine (Surmontil) is by far the most helpful in my experience, and I've tried a lot (including 4 SSRIs!).
But how or why does it work?
Like many drugs, it is an antagonist at histamine H1, serotonin 5-HT2A, and muscarinic acetylcholine receptors. It is also an antagonist at alpha1-adrenergic and histamine-H2 receptors, and less so at dopamine-D2 sites.
I propose that the main beneficial mechanisms of action are the histamine-H2 and muscarinic blockade. The histamine-H2 seems to be the only unusual target.
-undopaminergic
Posted by linkadge on October 9, 2020, at 15:25:35
In reply to How does trimipramine (Surmontil) work?, posted by undopaminergic on October 9, 2020, at 8:42:33
Muscarinic receptor antagonism, 5-ht2 receptor antagonism and possibly some other actions (ion channels, inflammation). There could be other actions like epigenetic modifications which go beyond the monoamines. It may also regulate the HPA axis independently of the above actions.
Who knows.
Linkadge
Posted by undopaminergic on October 10, 2020, at 2:56:38
In reply to Re: How does trimipramine (Surmontil) work?, posted by linkadge on October 9, 2020, at 15:25:35
> Muscarinic receptor antagonism, 5-ht2 receptor antagonism and possibly some other actions (ion channels, inflammation). There could be other actions like epigenetic modifications which go beyond the monoamines. It may also regulate the HPA axis independently of the above actions.
>
> Who knows.
>
> LinkadgeYou're right, it *is* an ion-channel antagonist. It numbs the mucous membranes of the mouth.
It may be relevant that famotidine (another histamine-H2 antagonist) has been used with some success for schizophrenia, the negative symptoms of which resemble depression:
https://www.google.com/search?q=famotidine+schizophrenia&oq=famotidine-undopaminergic
Posted by linkadge on October 11, 2020, at 16:49:25
In reply to Re: How does trimipramine (Surmontil) work?, posted by undopaminergic on October 10, 2020, at 2:56:38
I remember reading too, that similar to other TCAs, there is some effect on opioid systems. I think the TCAs might interact with enkaphalinase or something.
Linkadge
This is the end of the thread.
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