Anavex Life Sciences Corp (AVXL)

[falconer66a]

Thank you for your comments and observations.

Accurately, you stated:

Another thought I have, that I didn't see in your talk, is the belief that there are different consequences to be achieved by different agonists, ligands or activators; and that the actual result of activation of sr1 will differ depending on the cell function and location.

Yes, there are other molecules that will attach to the sigma-1 receptor protein. But I’ve said little about them. That’s because I know very little about them. I’ve checked, in a cursory fashion, what I can find about them and none of them have displayed either the safety or efficacies of blarcamesine. I’ve found no evidence that any of them can compete with the Anavex drug. No other molecules attaching to the sigma-1 receptor protein have ever yielded the therapeutic results of blarcamesine. Merely sticking to the sigma-1 receptor protein (being a ligand of it) isn’t sufficient. Lots of proteins stick to a lot of other proteins in cells. Chemically, proteins can be “sticky.” When blarcamesine sticks to the sigma-1 receptor, that combination can then favorably modulate and promote a diversity of downstream reactions and processes. So far, nobody else’s molecule can do this.

Then, you stated:

Furthermore, I'm not clear yet what part the muscarine receptors play, except I do think they are significant. They already are active elements in other drugs.

Good observation. I’ve never said much of anything about the muscarine receptors. It’s a topic I’ve not delved into for deep understanding. Blarcamesine, no doubt, can act on or as a muscarine receptor. But I admit ignorance of the phenomenon. I’ll let others more precisely describe the matter. Presently, blarcamesine’s activation of the sigma-1 receptor is sufficient, producing the favorable therapeutic outcomes. I invite the presentation of more detailed information on the muscarine factor.

I don’t see that blarcamesine’s operation on the sigma-1 receptor protein as a “vector force” phenomenon. I see it as a favorable reconfiguration of the shape and binding forces of the receptor, which consequently allows it to promote or facilitate the downstream reactions. A change in intramolecular binding forces, changing the shape of the receptor, allowing favorable new reactions to occur.

Soon enough, someone will gain a PhD, telling the deep chemistry of the involved molecules. It will explain things; but I don’t have enough organic chemistry to understand the muscarine matter in any depth. Nonetheless, blarcamesine will continue to function as a profound therapeutic agent. My ignorance of its involvement in muscarine activation is irrelevant.