6 replies to this topic

[PeopleProgrammer]

Nicotine has a powerful and documented nootropic effect through its nicotinic acetylcholine receptor agonism. Both nicotine and muscarine are highly toxic at high doses. Acetylcholine itself is highly nootropic. Could muscarine be equally powerful but work through the other subtype of acetylcholine receptors? I see a complete lack of commercial availability or interest in the mAchR system but an abundance in the nAchR system. perhaps this is misplaced?

Muscarinergic Acetylcholine receptor agonists have nootropic properties:

https://en.wikipedia...wiki/Xanomeline

https://en.wikipedia.org/wiki/CI-1017

https://en.wikipedia...wiki/Tazomeline

…As do positive allosteric modulators of these receptors:

https://en.wikipedia...wiki/77-LH-28-1

Also, some analgesic properties:

https://en.wikipedia...iki/Vedaclidine

Partial Agonists seem to lack significant nootropic effects:

https://en.wikipedia...ki/Talsaclidine

https://en.wikipedia...iki/Sabcomeline

https://en.wikipedia...wiki/Milameline

So, wouldnt muscarine be expected to posses all the benefits of other muscarinic acetylcholine receptor agonists?

[PeopleProgrammer]

There are 5 different types of muscarinic receptors; M1 - M5, and most tissues express a mixture of subtypes. The M2 and M3 subtypes mediate muscarinic responses at peripheral autonomic tissues. M1 and M4 subtypes are more abundant in brain and autonomic ganglia. M1, M3 and M5 interact with Gq proteins to stimulate phosphoinositide hydrolysis and the release of intracellular calcium. M2 and M4 receptors interact with Gi proteins to inhibit adenylyl cyclase, which results in a decrease of intracellular concentration of cyclic adenosine monophosphate (cAMP). none of them are coupled to ion channels. the release of intracellular calcium stores is generally insufficient to induce convulsions however it would worsen the neurotoxicity of a sudden influx of external calcium. thus, it would logically follow that muscarine and its affected acetylcholine receptors would not induce but may worsen convulsions or seizures. Muscarine has the advantage that it should posses the combined effects of an agonist at each individual receptor. it should be more powerful and have a better price-benefit ratio albeit with potentially greater side effects. 

[treonsverdery]

i am basically uninformed, my first reaction is that the receptor is named after the dangerous fungi (optional Vanilla ice reference), is the body response different than the brain response?  is the muscarinic acetylcholine receptor just as it is, risky?

 

perhaps a beneficial harmless nootropic could come from those receptors even though people think of the fungi.

Edited by treonsverdery, 07 July 2016 - 11:12 PM.

[PeopleProgrammer]

Just want to point out; the difference between a medicine and a poison is simply the dose. muscarine is highly dangerous in the high doses found in the mushroom for which it is named, just as nicotine is highly toxic in the concentrations found in tobacco and other members of the nicotiana genus.

 

 

speaking of harmless nootropics: Turns out the famed PRL-8-53 (and perhaps even the legendary PRL-8-147, in turn) is implicated in muscarinergic signalling. given the strong nootropic effect of agonists and the strong impairment produced by antagonistms of Muscarinergic acetylcholine receptors, it appears to be likely that PRL-8-53 is a high efficacy/affinity muscarinergic acetylcholine receptor agonist.

 

http://www.longecity...433#entry598433

[treonsverdery]

>Turns out the famed PRL-8-53 (and perhaps even the legendary PRL-8-147, in turn) is implicated in muscarinergic

 

I read some of the PRL-8-53 journal article

 

you are right about muscarnic recpetors having development potential as nootropics!

 

 

[sativa]

You can obtain a great acetylcholine based cognitive boost by combining nicotinic/muscarinic antagonsism followed by nicotinic/muscarinic agonism.

A good full spectrum muscarinic antagonist is scopolamine (present in datura seeds - I've used 3-5 datura stramonium seeds,keep the dose low!).

Memantine can provide alpha 7 nicotinic antagonsism.

Lobelia inflata can provide more nicotinic antagonsism.

For the nicotinic/muscarinic agonism an acetylcholinesterase inhibitor would be perfect. (I use either Celastrus Paniculatus, Taspine from dragons blood 8:1 extract. Rosemary, lemon and pine oil would also work)

[PeopleProgrammer]

something worth considering is that muscarine is no longer believed to be the principal danger in amanita muscaria:

 

https://en.wikipedia...ia#Pharmacology

 

Thus, muscarine should not be considered dangerous based on the fungus. It turns out that we were all incorrect in our collective assumption about muscarine.

Edited by PeopleProgrammer, 19 July 2016 - 10:54 PM.