Anavex Life Sciences Corp (AVXL)

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Anavex Molecules are Sigma-1 Receptor Agonists, Not Antagonists

Very interesting and important article. Thanks for posting it. It strongly suggests viable cellular targets to turn off opioid compulsions.

The article tells of the involvement of sigma-1 and sigma-2 receptors in opioid and other psychoactive drug activities within various cells, particularly within the brain.

But the focus is the suggested usefulness (very strong) of sigma-1 or sigma-2 receptor antagonists, new molecules that would disrupt or disable normal sigma receptor functions in the presence of opioids or other drugs.

This is exactly the opposite of what the Anavex molecules do. They are (to my understanding) all agonists, molecules that facilitate or promote normal or restored cellular functions. The target molecules in the article are sigma receptor antagonists, molecules that would disable or suppress normal sigma receptor functions. In the presence of opioids or psychoactive drugs, this would be beneficial.

As far as I know, Anavex doesn’t have any sigma receptor antagonists, only agonists.

But one very important concept was described, the exact parallel of sigma receptors in rats and mice and humans:

s1-receptors have been cloned with high homology and identity from several species, including rodents and humans . The s1-subtype is a 223-amino acid protein with two transmembrane domains . It represents a unique structural class of proteins that possess chaperone-like functions . Within cells, s1-receptors can be found on the endoplasmic reticulum, mitochondria, nuclear membrane envelope and plasma membrane ; their localization at the interface of the endoplasmic reticulum and mitochondria has become the focus of recent research. Following the binding of ligands to it, the s1-receptor can translocate between different cellular compartments and form protein–protein interactions to modulate the activities of G-protein-coupled receptors (GPCR), ion channels and signaling molecules .

A lot of cell science terminology, in essence, this. “Homology” means same structure and function, here in rats, mice and humans. The paragraph reiterates that the sigma receptor structure and functions in murines (rats and mice) are exactly parallel and identical to humans.

Does this mean anything useful for those of us watching the development of the Anavex story? Indeed. The extensive lab work done on murines, where Anavex molecules successfully and safely treated a good number of difficult neurological (and other) diseases is evidence of similar results to occur in humans. The molecular, cellular structures in both rodents and humans are virtually identical, as will be the clinical results.