Anavex Life Sciences Corp (AVXL)

[georgejjl]

falcobner66a

DM is an uncompetitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, a sigma-1 receptor agonist, and a serotonin and norepinephrine reuptake inhibitor.

https://www.ncbi.nlm.nih.gov/pubmed/26000221

A study using positron emission tomography have demonstrated that an oral administration of fluvoxamine or donepezil could bind to sigma-1 receptor in the healthy human brain, suggesting that sigma-1 receptor might be involved in the therapeutic mechanisms of these drugs.

In clinical studies, some sigma-1 receptor agonists, including fluvoxamine, donepezil and neurosteroids, improve cognitive impairment and clinical symptoms in neuropsychiatric diseases.

https://www.ncbi.nlm.nih.gov/pubmed/22288409

Anavex 2-73 works better because Anavex 2-73 activates both the sigma 1 receptor and the muscarinic M1 receptor to facilitate preventing and clearing misfolded proteins at the endoplasmic reticulum among other benefits such as improving mitochondrial functioning.

ANAVEX2-73 acts both as a potent muscarinic compound,
with Ki values lower than 500 nM for all M1–M4 subtypes and
as a moderate s1 receptor agonist

http://anavex.com/files/Anti-amnesic%20and%20neuroprotective%20potentials%20of%20ANAVEX2-73.pdf

Quite possibly and probably Anavex's crown jewel in Anavex 3-71 fromerly AF710b

...orders of magnitude more potent than donepezil (Aricept) and other agonist acting eithe on M1 or the sigma 1 receptors, respectively Anavex 3-71 (formerly AF710b)

For those of you that may not be familiar with the term " orders of magnitude, this means that Anavex 3-71 is probably 3 or 4 orders of magnitude (one thousand to ten thousand times) more potent than donepezil (Aricept) or any other similar agonist known to date.

https://en.m.wikipedia.org/wiki/Order_of_magnitude

In Zuers, both Fisher and Maurice presented their respective efforts at finding small molecules that tickle this receptor in a way that might treat AD better than current drugs do. Fisher introduced AF710B, a bicyclic heterocyclic spiro-compound that he said selectively activates both the muscarinic M1 receptor and the s-1 receptor. In detailing its effects on a list of phenotypic parameters—it increases sAPPa secretion, decreases tau hyperphosphorylation and GSK-3ß activity, decreases Bax, and increases BCL2 expression in mitochondria—Fisher emphasized that the former two effects come through the M1 receptor and the latter two through the s-1 receptor. Unlike previous compounds Fisher developed, which were mainly M1-selective orthosteric agonists, AF710B is an allosteric M1 receptor agonist. Its heteromer-specific effects differentiate it from other M1 agonists and modulators. Fisher claimed that the new compound is exquisitely potent, acting as a cognitive enhancer in rats at 1 to 30 micrograms (not milligrams) per kilogram body weight. According to Fisher, the compound is orally available with a safety margin of more than 50,000 times the minimally active dose. “Those are orders of magnitude more potent than donepezil and other agonists acting either on the M1 or the s-1 receptors, respectively,” Fisher said

http://www.alzforum.org/news/conference-coverage/zuers-alpha-beta-sigma-which-will-yield-new-ad-drug

Shalom

Good luck and GOD bless,

George