Posted by linkadge on December 29, 2019, at 13:30:50
In reply to Re: Anticholinergics as antidepressants » linkadge, posted by undopaminergic on December 29, 2019, at 10:45:27
>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.
Well, if we're going to pick :) It's hard to know whether a drug of abuse would be 'more' abusable under different circumstances. Pure dopamine reuptake inhibitors likely don't have the same abuse potential as cocaine (a triple reuptake inhibitor with monoamine releasing capacity). Even in DAT knockout mice, cocaine still exhibits rewarding effects, arguing against the notion that the dopamine transporter is solely responsible for cocaine's actions. Yes, I head that benztropine acts on the dopamine transporter in a different way from cocaine, but this doesn't mean that it doesn't still increase dopamine levels in the synapse. I found benztropine much 'better' than say dimenhydrinate (which I find pretty discussing to be honest).
>I've also tried Scopoderm (scopolamine) patches, >and I felt slightly better, but I had to quit due >to skin irritation.
I've used the scopolamine patch (a bit expensive here in Canada) for depression. However, I didn't find it practical for longer term use as it left me feeling a bit detached. Again, not as 'good' as benztropine.
>I read that 5-HT2A antagonists acutely increase >dopamine release in the prefrontral cortex, but >with chronic administration, this effect is not >sustained.
Hmm. Any references on that? I suppose it depends on whether 5-ht2a receptors upregulate or downregulate in response. Not all 5-ht2a antagonists function the same way. Atypcal antipsychotics can 'normalize' cognition in schizophrenia (in some studies) an effect that is presumably due to 5-ht2a antagonism. I haven't heard of this effect 'wearing off' but who knows. 5-ht2a and 5-ht2c antagonists can also produce neurotrophic effects, and increase slow wave sleep / melatonin release.
>It does, acutely, and then there is a rebound >(ie. increased cortisol) effect.
Any references to this? Do you mean a rebound when the drug wears off, or when it is still in the system? Ideally you want cortisol to be lower in the evening / night and then increase in the morning. Persistently low cortisol is not a good thing and can make you feel worse.
>I'm afraid not. It did not change the ACTH >(adrenocorticotropic hormone) levels in the >study/ies I read.
Any reference to this? I can't find any evidence of a cortisol rebound effect.
https://www.ncbi.nlm.nih.gov/pubmed/19038406
https://www.ncbi.nlm.nih.gov/pubmed/9160649
https://www.ncbi.nlm.nih.gov/pubmed/1661430Here's a study on the d2/d3 receptor upregulation following trimipramine administration. This sets it apart from mirtazapine, which does not induce this upregulation. I found that trimipramine had a much stronger effect than mirtazapine on my core anhedonia. On paper, mirtazapine and trimipramine should induce similar effects, but they apparently don't. Many antidepressants (and ECT) increase the sensitivity of the d2/d3 receptor system.
https://www.ncbi.nlm.nih.gov/pubmed/9660111
Linkadge
poster:linkadge
thread:1107464
URL: http://www.dr-bob.org/babble/20191019/msgs/1107487.html