Talk:Muscle-type nicotinic receptor

message: Should we list other agonists such as nicotine and epibatidine? Also, what about adding a list of partial agonists?Shanata (talk) 07:18, 14 October 2010 (UTC)
thread_title:  Other agonists and partial agonists 

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thread_title:  External links modified (February 2018) 

message: Until recently, my knowledge was that the fetal receptor gets replaced entirely by its adult counterpart as the neuromuscular junction matures, and as a result, the fetal type will only be expressed in denervated muscles and during fetal development (hence its name!) but not play any role in the function of intact neuromuscular junctions.
However, this seems to be accurate in rats and mice but not in humans. According to a few studies on congenital myasthenic syndromes, the healthy human NMJ does indeed retain a small number of fetal-type receptors which increase the chance of survival in forms of CMS where the epsilon subunit is mutated.
https://pubmed.ncbi.nlm.nih.gov/11408331/
Besides, mice and rats seem to continue expressing the fetal receptor at small numbers in extraocular muscles but not anywhere else. Which won't help them survive in case of CHRNE mutations as it doesn't prevent or alleviate respiratory failure.
Nevertheless, many papers on NMJ development use rodent models and generalize them to humans, apparently without regard for these differences. Similarly for studies on pharmacologic agents and neurotoxins, as a few of them interact differently with fetal and adult muscle nAChRs.
Aren't any other "suitable" laboratory animals known which have more human-like NMJs? (Maybe organoids?)
Anyway, if this is indeed true (sufficiently reproduced) it may be worth mentioning in the article. --2003:E7:7706:7A82:88BC:61A9:9444:D598 (talk) 21:13, 14 April 2022 (UTC)
thread_title:  persistence of fetal receptor type in healthy human muscle? 

message: Despite their therapeutic potential, allosteric modulators of this receptor are indeed not well-known. However, there seem to be some drugs used for entirely different purposes which do this as a side effect.
For example, here is a paper on monoamine uptake inhibitors interacting with muscle and neuronal nAChRs, and if I understand the abstract correctly, those act as negative allosteric modulators at the muscle nAChR:
https://pubmed.ncbi.nlm.nih.gov/11526465/
Similarly for endogenous serotonin, at least according to the first "similar article" in the list below. 
Importantly, these are studies on rodent NMJ models again, which in the absence of detailed knowledge about the mechanism may or may not generalize to humans.
There are also papers examining the influence of general anaesthetics and other drugs on neuromuscular block during general anaesthesia. What I remember form those is that certain substances influence the binding of the neuromuscular blocking agents to the receptor. E.g. nitrous oxide and xenon tend to increase binding affinity and thus the onset and duration of neuromuscular block. Do they do this only to antagonists, or to acetylcholine as well? In the latter case they would qualify as PAMs. (The alleged ethymology of the name "laughing gas" for nitrous oxide stemming from diaphragm spasms would fit to such a mechanism of action, at least.) --2003:E7:7706:7A82:88BC:61A9:9444:D598 (talk) 22:03, 14 April 2022 (UTC)
thread_title:  PAMs and NAMs