Shouldn't anti cholinergic effect fade in a few days due to receptor upregulation? This is what happens with memantine that I'm taking now. Worsening dyslexia initially but not noticeable a week later.
Well, it depends on the mechanism, strength of said mechanism, and the biological curiosities of the subject in question - not everyone experiences the anticholinergic side-effects of Wellbutrin at all - yet some, like me, seems to be continously susceptible to it.
Perhaps we have a permanent overplethora of Cholinergic receptors? In my case, I have genes controlling nicotinic receptors which proposes that I am more likely to become dependent. Maybe part of that is because I have some mechanism in me which prevents receptor up and deregulation to some extent?
There is a high variability to susceptibility to these side-effects - and most people don't even seem to notice the anticholinergic effects - so they must obviously have highly differing receptors from those that do.
There is actually, shockingly enough, people that can use even GABA-ergics like Benzo's for years on end, without any seemingly greater loss of efficacy.
I actually dug up some interesting studies on tolerance to Benzodiazepines - the tolerance-developing "standard" of medicine, if you like.
Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-Selective Receptor Modulators?
http://www.hindawi.c...ps/2012/416864/
It seems like tolerance does not develop the same way in receptors that are affected by the same neurotransmitters even - rather interesting fact, because it makes the resistance of the D4-receptors to up and de-regulation no longer seem like such an unusual feature - there are other receptors with this behaviour as well.
Ey, I even found an article regarding resistance towards down-regulation of GABA-receptors! Check it out. I am going to assume that a similar mechanism may be involved in those of us that don't experience any greater anticholinergic tolerance - I'm guessing it's specifically one of the nicotinic subunits - since I actually did develop tolerance to the hypnotic effects of Promethazine (lergigan) to some extent. (still had god-awful hangover the next day, it just didn't put me to sleep. Which implies that some of the anticholinergic effects remained)
Figure 5: siRNA-resistant GABAB2 rescues phenotypes associated with wild-type GABAB2-subunit downregulation.
http://www.nature.co...mms2820_F5.html
Edited by Stinkorninjor, 24 July 2016 - 02:53 PM.