Anavex Life Sciences Corp (AVXL)

[falconer66a]

Yes, Aricept attaches to the sigma-1 protein. But....

Aricept is also a high affinity S1R agonist.

Well, as you surely know there are a good number of molecules that are sigma-1 receptor ligands. But their individual abilities to effectively activate or facilitate sigma-1 receptor functions are highly variable.

Aricept's Alzheimer's therapeutic outcomes derive from its ability to suppress the catalytic activity of acetylcholinesterase; not because it effectively activates the sigma-1 receptor protein. The "high affinity" merely indicates that Aricept readily or strongly binds to the sigma-1 receptor protein; not that that it thusly produces any therapeutic effects of note.

There are a multitude of molecules that can bind to the sigma-1 receptor protein; are ligands to that molecular binding site. But none of them, neither in preclinical murine nor in early clinical human trials have produced the Alzheimer's symptom-resolving outcomes of blarcamesine. The sigma-1 receptor ligand that best activates that protein's cell-keeping functions is clearly blarcamesine. If Aricept worked as an effective ligand on the sigma-1 receptor protein Alzheimer's patients taking that drug wouldn't find that after a certain period their symptoms resumed and progressed to a lethal end.