Posted by undopaminergic on December 29, 2019, at 10:45:27
In reply to Re: Anticholinergics as antidepressants » undopaminergic, posted by linkadge on December 27, 2019, at 17:11:02
> Anticholinergics can be antidepressants. Benztropine can be abused (euphorogenic effects).
>I agree, but it probably does not work for everyone.
> Benztropine is also a dopamine reuptake inhibitor as well as anticholinergic.
>From what I've read, it does bind to the dopamine transporter, but it is atypical, and does not bind to the same site as cocaine or methylphenidate. If it did, we can be pretty sure it would be even more of a drug of abuse.
> I purchased some belladonna extract. You've got to be careful...one single drop can be felt!
>Sounds like a particularly potent extract. I've tried leaves of Angel's Trumpet (Brugmansia), as well as atropine eyedrops, to dilate my pupils, for example to counteract the miosis of buprenorphine. I've also tried Scopoderm (scopolamine) patches, and I felt slightly better, but I had to quit due to skin irritation.
> I would say that the anticholinergic effects of TCAs add to their antidepressant effects.
>Right.
> They can also reduce side effects (i.e. akathisia).
Yes, and they cause some other side effects, such as dry mouth.
> Trimipramine is also a 5-ht2 antagonist which can have antidepressant effects.
>I read that 5-HT2A antagonists acutely increase dopamine release in the prefrontral cortex, but with chronic administration, this effect is not sustained.
> Some of its metabolites have some impact on DAT and MAO-B.
>That is very interesting. Do you know where you found out about it? I made a pretty thorough review of the literature when I was investigating trimipramine, and I don't recall anything about DAT or MAO-B.
But according to Wikipedia, trimipramine may antagonise dopamine autoreceptors (presynaptic).
Notably, it is also a potent histamine H1- and H2-receptor antagonist. The H2 action is exciting, because famotidine (a selective H2-antagonist) in some studies helps to ameliorate negative symptoms of schizophrenia.
> There may be some additional (yet unidentified) mechanism common to the TCAs (I.e. anti-inflammatory, or epigenetic).
>Well, I discovered that it (trimipramine) is an antagonist at some ion-channels (probably sodium ones). I tried to take it sublingually and it numbed the parts of my mouth it came into touch with. The local anaesthesia took so long to dissipate that I began to worry that it had done permanent damage, destroying parts of my sense of taste. Thank goodness there was a happy ending.
> Trimipamine likely has anticortisol effects
>It does, acutely, and then there is a rebound (ie. increased cortisol) effect. It has been shown, when taken at night, to normalise the circadian cortisol level curve, which is abnormal in some depressions such as burnout.
Other TCAs seem to have opposite effects on cortisol.
> and may affect HPA axis at a more fundamental level.
>I'm afraid not. It did not change the ACTH (adrenocorticotropic hormone) levels in the study/ies I read.
> Trimipramine elevates the expression of D2 and D3 receptors (common to many antidepressants, but not mirtazapine). I believe it interacts with opioid systems like other TCAs.
>I was not aware of that. Maybe it could be combined with pramipexole.
-undopaminergic
poster:undopaminergic
thread:1107464
URL: http://www.dr-bob.org/babble/20191019/msgs/1107485.html