Replies to post #257900 on Anavex Life Sciences Corp (AVXL)

[Doc328]

A273 is an agonist at the sigma1, M1, M2, M3 and M4 receptor (A371 is an S1R agonist and M1 positive allosteric modulator)

Donepezil is an agonist at sigma1 and an acetylchlolinesterase (AChE) inhibitor. Acetylcholine acts at the nicotinic acetylcholine receptor and all muscarinic acetylcholine receptors (M1 through M5) as the natural agonist. AChE normally works by metabolizing (breaking down) ACh at the synapse which inactivates it. Thus, donepezil partially inactivates AChE and allows ACh to last longer at the synapse which leads to longer activity of ACh at the M1-M5 receptors (some ACh will be broken down still by another enzyme BuChE and some ACh will diffuse away). Hence, there is significant overlap in mechanism of action between the drugs though the differences still make predicting outcome uncertain