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Re: pcguy post# 255512

Saturday, 06/20/2020 8:45:52 PM

Saturday, June 20, 2020 8:45:52 PM

Post# of 459915
Yes, muscarinic receptors do play a role as you say, and with Parkinson’s as well. There is a need to explore and know more about this, and Anavex may be taking one of the first steps in doing so with the PDD study. If I may add, this:

AVXL 2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors. It is a mixed ligand for sigma1/muscarinic receptors. SEE: https://www.alzforum.org/therapeutics/blarcamesine

I have located a couple of references, but only about M1.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286317/

Roles of the M1 Muscarinic Acetylcholine Receptor Subtype in the Regulation of Basal Ganglia Function and Implications for the Treatment of Parkinson's Disease

2. https://www.michaeljfox.org/grant/highly-selective-m1-muscarinic-receptor-positive-allosteric-modulators-treatment-parkinsons

Hypothesis:
We believe that small molecules that affect the function of the M1 mAChR in a highly selective manner have the potential to deliver novel, well-tolerated and efficacious drugs to treat learning and memory deficits in individuals with PDD.

Study Design:
We have generated small molecules of novel chemical classes that are positive allosteric modulators of the M1 mAChR and have a good understanding of the structure-activity relationship of these molecules. Based on this knowledge, we will synthesize these molecules and optimize them for target engagement in the brain and safety.
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