34 replies to this topic

[CWF1986]

^

 

That article suggests that what I'm saying is correct.  7th paragraph down.  

 

My personal experience with Wellbutrin is that it makes me super spacey and kills my working memory the first few days, then it returns to baseline, then it improves over baseline.

 

The only reason I don't take it now is because it doesn't play well with Adderall for me and I find the Adderall more important treatment.  

 

And for those that say tricyclics are the devil, nortriptyline and desipramine arguably don't have any worse sides than many SSRIs. They in part act as mAChR antagonists granted much less than first generation tricylcis and this may very well be part of their mechanism of action.

 

Strattera was made with the intentions of mimicking the antidepressant effects of tricyclics, but without the side effects.  They succeeded in eliminating any significant mAChR antagonism effects, but failed in making an effective antidepressant.  Is this because the mAChR antagonism was taken away?  There is evidence to suggests so, but the question isn't concretely answered at this time.  

 

I take nortriptyline myself and it actually improves my working memory.  Is it the NE reuptake?  Or just because it helps with anxiety and depression?  It's hard to say.  

 

I know I have to avoid anything increase mAChR activity because it'll cause me deep despair and constant looping of the bad things from the past and constant worrying of the past and a general unhealthy level of distrust.  It does go away once whatever I took leaves my system.  Even soy lecithin does this to me, granted not as much as say huperzine.  

 

This is an atypical response so for anyone reading this don't assume this will happen for you.  Cholinergics may very well be something to make you cognitively sharper and/or able to kill it in the gym.  

 

My main point is that it's not as simple as anticholinergic bad, cholinergic good.  It gets pretty complex pretty fast.  Ultimately, you just have to find out what works for you.  Make a log of everything you take, give it a fair trial, then assess your log and look for patterns.  I do this for new prescriptions and supplements.  It helps a lot.  

Edited by CWF1986, 05 August 2017 - 06:22 AM.

[rian]

^

 

That article suggests that what I'm saying is correct.  7th paragraph down.  

 

My personal experience with Wellbutrin is that it makes me super spacey and kills my working memory the first few days, then it returns to baseline, then it improves over baseline.

 

The only reason I don't take it now is because it doesn't play well with Adderall for me and I find the Adderall more important treatment.  

 

And for those that say tricyclics are the devil, nortriptyline and desipramine arguably don't have any worse sides than many SSRIs. They in part act as mAChR antagonists granted much less than first generation tricylcis and this may very well be part of their mechanism of action.

 

Strattera was made with the intentions of mimicking the antidepressant effects of tricyclics, but without the side effects.  They succeeded in eliminating any significant mAChR antagonism effects, but failed in making an effective antidepressant.  Is this because the mAChR antagonism was taken away?  There is evidence to suggests so, but the question isn't concretely answered at this time.  

 

I take nortriptyline myself and it actually improves my working memory.  Is it the NE reuptake?  Or just because it helps with anxiety and depression?  It's hard to say.  

 

I know I have to avoid anything increase mAChR activity because it'll cause me deep despair and constant looping of the bad things from the past and constant worrying of the past and a general unhealthy level of distrust.  It does go away once whatever I took leaves my system.  Even soy lecithin does this to me, granted not as much as say huperzine.  

 

This is an atypical response so for anyone reading this don't assume this will happen for you.  Cholinergics may very well be something to make you cognitively sharper and/or able to kill it in the gym.  

 

My main point is that it's not as simple as anticholinergic bad, cholinergic good.  It gets pretty complex pretty fast.  Ultimately, you just have to find out what works for you.  Make a log of everything you take, give it a fair trial, then assess your log and look for patterns.  I do this for new prescriptions and supplements.  It helps a lot.  

Thanks again, man.

 

So you're saying despite it's anti-nicotinic properties, bupropion is not really anti-cholinergic? sorry to probably ask that dump, but i'm not really into this topic. I simply wanna know if Bupropion blocks acetylcholine? And if so, how strong. Im also not that much interested in some kind of cognitive boost.

 

More so, my concern is in terms of digestion: i had one pill of bupropion and it fucked up my digestion. in fairness, i probably built a decent fuck up basis by taking ssris before. did you yourself experience some kind of slower digestion with bupropion (cause acetylcholin is known to be responsible for gut motility. I mean i still can go once a day, but normally i would defecate 2-3 times.

 

sure, the bupropion could have just cumulate the effects of sertralin and escitalopram (which i took before, see the story here: http://www.longecity...t/#entry823132)but significant is, that now after bupropion, the digestive problems did not go away (as they did with the ssris). 

 

Do you happen to know some anticholinergic values for the likes of sertralin or citalopram (compared to bupro).

 

Thanks again, you helping me a lot!

 

Hope my non-native english doesnt bother you that much

[CWF1986]

In the wiki page for bupropion, it says it's a negative allosteric modulator for the 5ht3 receptor.  The 5ht3 receptor is found mostly in the brain stem and controls functions such as nausea, increased gut motility, vomiting, and gut secretions.  An agonist of this site will increase the amount of the aforesaid effects.

 

A negative allosteric modulator will decrease downstream effects.  So a negative allosteric modulator of the 5ht3 receptor will likely decrease gut motility to the point that it may cause constipation.  

 

The 5ht3 site is very similar to some of the nicotinic acetylcholine sites which bupropion is an antagonist of so from that point of view, it really shouldn't be too surprising that bupropion might effect the 5ht3 site.

 

So to answer whether or not the nicotinic anticholinergic effects of the bupropion are causing constipation the answer is no.  

 

And comparing the acetylcholine effects of those two ssri's is not the best question for finding the answer you're looking for which I believe is how to fix the constipation.  Those two ssri's might have very very low affinity for the muscarinic acetylcholine receptor sites, but they are largely clinically irrelevant and just as importantly if not more so the muscarinic and nicotinic acetycholine receptors have very different effects.

 

Always remember that their are two acetylcholine sytems.  One the is the nicotinic and the other is the muscarinic and they have very different effects on the body and brain.  

 

So yes, bupropion is an anticholinergic, but the type of anticholinergic effects from it are from antagonism of nicotinic receptors and to my knowledge, that won't cause decreased gut motility.  However, antagonism of muscarinic acetylcholine sites can cause constipation hence why it can be a side effect of tricyclic depressants which are machr antagonist.  

 

If you want to try to address the 5ht3 receptor, than you will need something that will increase downstream effects of the receptor.  I'm not sure if anything can selectively do this. 

 

It might be better to try more traditional way to increase gut motility first before you use something with broad spectrum effects in an effort to target the 5ht3 receptor.  

[rian]

In the wiki page for bupropion, it says it's a negative allosteric modulator for the 5ht3 receptor.  The 5ht3 receptor is found mostly in the brain stem and controls functions such as nausea, increased gut motility, vomiting, and gut secretions.  An agonist of this site will increase the amount of the aforesaid effects.

 

A negative allosteric modulator will decrease downstream effects.  So a negative allosteric modulator of the 5ht3 receptor will likely decrease gut motility to the point that it may cause constipation.  

 

The 5ht3 site is very similar to some of the nicotinic acetylcholine sites which bupropion is an antagonist of so from that point of view, it really shouldn't be too surprising that bupropion might effect the 5ht3 site.

 

But if Bupro is a negative allosteric modulator, which decreases gut motility, why are u stating here 

So to answer whether or not the nicotinic anticholinergic effects of the bupropion are causing constipation the answer is no.  

 

that Bupro wont cause constipation. Or do u mean its anticholinergic properties wont cause constipation, but the other mentioned properties will do!?

 

 

And comparing the acetylcholine effects of those two ssri's is not the best question for finding the answer you're looking for which I believe is how to fix the constipation.  Those two ssri's might have very very low affinity for the muscarinic acetylcholine receptor sites, but they are largely clinically irrelevant and just as importantly if not more so the muscarinic and nicotinic acetycholine receptors have very different effects.

 

Yea nah, I'm trying a lot of ways to fix the constipation. My question there was more aimed towards if the two ssris i took before for a long time did their contrubution to the digestion problems im experiencing now. Do you have any information about the muscarinic anticholingergic/5ht3 effects of sertralin and escitalopram? or are those two even negative allosteric modulators, too?

 

Im just trying to find out, if the one pill I took from Bupro kind of cumulated the effects of the ssris, i took before. Or if they're having different properties concerning gut motility.

 

From my understanding, ssris like escitalopram and sertralin are a 5ht3 agonist, thus should for example increase gut motility, right? Which leads to me the question: why does Bupro has serotonergic effects, as it only targets dopamin and noradrenalin!?

 

 

So yes, bupropion is an anticholinergic, but the type of anticholinergic effects from it are from antagonism of nicotinic receptors and to my knowledge, that won't cause decreased gut motility.  However, antagonism of muscarinic acetylcholine sites can cause constipation hence why it can be a side effect of tricyclic depressants which are machr antagonist.

 

But as you mentioned before, the Bupropions effect on the 5ht3 site would cause constipation, though? So if not from it's anticholinergic activities, Bupropion will/can still cause constipation?

 

 

Thanks again man! We're getting closer for me to fully understand it

Edited by rian, 08 August 2017 - 11:02 AM.

[Kinesis]

Arguably, the nicotinic acetylcholine antagonism at specific nAChRs is a major part of the antidepressant effect of wellbutrin. If you're taking it for depression, it very well might reduce the antidepressant effect of wellbutrin.

https://www.ncbi.nlm...pubmed/19497387

https://www.hindawi....wj/2012/104105/

I've read more studies on the subject, but that's what I found in just few minutes. The first study is specifically about bupropion and the second is about possible antidepressant effects of nAChR antagonists and agonists in general.

Much thanks!

So by having an anti-nicotinic property it means bupropion is anticholingeric, right? I am not that much in the topic to understand much from the links :l

Why do so many sources claim the opposite. Like here: http://psychopharmac...hopharmacology/


Would love to have some insight from you, as you seem to be very knowledgeable

Antinicotinic may be the better word. Even the study cited in support of bupropion’s ostensibly anticholinergic properties doesn’t use the word “anticholinergic “ in connection with bupropion.