Comment · Sun, March 10, 2013 · Ceretropic
Questions about acetylcholine receptor antagonism and various interactions
Original post in this thread
amirrorbehind · 1 points
I take Tramadol and I'm trying to understand what exactly it's doing to my body and what I might stack with it to alleviate anything unwanted.
* What are, in general, the consequences of acetylcholine receptor antagonism? By preventing ACh from binding from its receptors (nicotinic [alpha-7] and muscarinic [m1, m3]) is ACh actually not doing its job? Or doing its job less?
* Should I be supplementing choline in this situation? It seems like antagonism would prevent choline (and then ACh) from performing its functions, so perhaps choline supplementation would be a waste?
* In this situation, what would an acetylcholinesterase inhibitor do? I'm looking at Huperzine-A.
I'm looking at the table just under here[1] and I'm wondering, for M1 and M3, by antagonising these receptors, am I preventing those actions from occuring ? Or at least somewhat?
[1] http://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptor#Difference_in_G_proteins
Thanks for any and every response :).
What they were answering
eluusive · 1 points
If you are antagonizing the receptors, then adding in more choline or preventing it's breakdown is not going to be effective. You need substances that allosterically modulate the ACh receptors, or indirectly lead to increases in muscarinic receptor transmission. Luckily, most of the racetams have been proven to reverse ACh receptor antagonist effects, as most are tested against scopolamine. This may lower the effectiveness of the Tramadol, though. What are you using it for?
You are assuming 100% blockade by Tramadol. This is not what happens. If ACh and Tramadol have the same affinity -- and it's blocking even 50% -- and you could theoretically double the amount of free ACh by some means -- the probability of binding to the remaining 50% of sites and activating those receptors remains roughly constant.
Remember, this is all probabilities -- and the two substances are competing for time at the receptor sites.
u/MisterYouAreSoDumb · Ceretropic
True, we don't know the relative affinities. And we have no idea what kind of up-regulation would happen due to that antagonism. It's just speculation at this point.