Below a couple of good posts IMO by falconer66a,
Fletch
falconer66a Sunday, 08/16/20 03:14:19 PM
Re: nidan7500 post# 265554 0
Post # of 265588
Decidedly, Anavex is different, better.
Thanks for posting this. I read the article in a quick first-read. It was published a year ago, but refers, in the case of Anavex, to clinical trials then still in early progress.
The general perspective of the author was that there are, indeed, a number of drugs that bind to the sigma-1 receptor protein, and they may eventually show some level of efficacy against various CNS diseases. At this point, accurate.
But what the author fails to understand, or elects not to state, is that the sigma-1 receptor agonists of Anavex Live Sciences Corp, primarily Anavex 2-73 (blarcamesine) and Anavex 3-71, are not equivalent to the several other agonists he mentioned (fluvoxamine, donepezil, haloperidol, and pentazocine). In fact, no comparison.
Yes, a number of molecules can bind to the sigma-1 receptor protein, and to some degree activate it, allowing it to more formidably modulate a multitude of cellular processes. But, simply, the Anavex molecules do this far more strongly and effectively.
First, the drugs have to get into the cells to work. Cells have a variety of ways of keeping most molecules and ions out. The Anavex molecules are small, and have chemistries that allow them to diffuse into neurons. Not a simple task. One of the reasons the other sigma-1 receptor agonists are not as effective may be because few can gain entry into target cells .
Not a problem with the Anavex molecules. Importantly, blarcamesine is administered peroral, by mouth. Not by an injection that by-passes the gastrointestinal system to get adequate concentration into the blood stream. That happens sufficiently by merely getting the drug into the stomach, where it is not lost or digested. It diffuses into the blood stream, then into cells throughout the body.
This will be particularly true with Anavex 3-71, as preclinical murine tests have shown that dosages are measured in micrograms, not the milligrams with blarcamesine. That's a factor of a thousand less. One-thousand micrograms in a single milligram.
Therefore, Anavex 3-71 has at least two things going for it. It is apparently much better at diffusing into cells. Dosages are much, much lower. Then, at those tiny doses, profound therapeutic outcomes are induced. Lastly, because of the tiny doses, chances for side effects are minimized, if not altogether obviated.
So, no comparison between the Anavex sigma-1 receptor agonists, compared to the others mentioned in the article. Big, powerful Anavex apples, compared to shrinking, moldy oranges.
When clinical results appear from any of the three Anavex trials, it will no longer be accurate or appropriate to lump all sigma-1 receptor agonists together. Clearly, the Anavex molecules will be revealed as a separate, exemplary category — to begin to successfully treat CNS and other diseases.
falconer66a Sunday, 08/16/20 04:17:29 PM
Re: abew4me post# 265574 0
Post # of 265588
Unique, favorable molecular architectures.
Quote:
And the phenomenal biochemistry comes from?
The Anavex sigma-1 receptor agonists, Anavex 2-73 (blarcamesine) and Anavex 3-71, are shaped like none of the other, less favorable sigma-1 receptor agonists (those mentioned in the article).
Understand, small proteins (such as the sigma-1 receptor) are flexible, malleable; able to be re-shaped or re-configured by the interplay of the multiple adhesive forces between the protein and any attached ligands, other properly-fitting molecules (such as those of Anavex).
In cellular biochemistry, shape is everything. When a modulating molecule such as the sigma-1 receptor is bent out of its properly-functioning shape (which apparently can happen with age or genetic factors), chemical reactions controlled or modulated by the molecule don't happen as often or as thoroughly. In the case of neurons with poorly-shaped sigma-1 receptor proteins, various pathologies result (including Alzheimer's, Parkinson's disease dementia, and Rett syndrome). The Anavex molecules bind to the sigma-1 receptor proteins, and thereby re-shape them to full chemical functionality, allowing them to subsequently modulate a variety of ensuing chemical reactions and processes, all of which restore chemical homeostatic processes within the neuron. The neuron is reverted to a more youthful, more fully functional status.
It's the shape. Simply, the Anavex molecules shape things up inside aging or genetically mal-affected neurons.
https://investorshub.advfn.com/boards/read_ms...=157658053
Fletch
falconer66a Sunday, 08/16/20 03:14:19 PM
Re: nidan7500 post# 265554 0
Post # of 265588
Decidedly, Anavex is different, better.
Thanks for posting this. I read the article in a quick first-read. It was published a year ago, but refers, in the case of Anavex, to clinical trials then still in early progress.
The general perspective of the author was that there are, indeed, a number of drugs that bind to the sigma-1 receptor protein, and they may eventually show some level of efficacy against various CNS diseases. At this point, accurate.
But what the author fails to understand, or elects not to state, is that the sigma-1 receptor agonists of Anavex Live Sciences Corp, primarily Anavex 2-73 (blarcamesine) and Anavex 3-71, are not equivalent to the several other agonists he mentioned (fluvoxamine, donepezil, haloperidol, and pentazocine). In fact, no comparison.
Yes, a number of molecules can bind to the sigma-1 receptor protein, and to some degree activate it, allowing it to more formidably modulate a multitude of cellular processes. But, simply, the Anavex molecules do this far more strongly and effectively.
First, the drugs have to get into the cells to work. Cells have a variety of ways of keeping most molecules and ions out. The Anavex molecules are small, and have chemistries that allow them to diffuse into neurons. Not a simple task. One of the reasons the other sigma-1 receptor agonists are not as effective may be because few can gain entry into target cells .
Not a problem with the Anavex molecules. Importantly, blarcamesine is administered peroral, by mouth. Not by an injection that by-passes the gastrointestinal system to get adequate concentration into the blood stream. That happens sufficiently by merely getting the drug into the stomach, where it is not lost or digested. It diffuses into the blood stream, then into cells throughout the body.
This will be particularly true with Anavex 3-71, as preclinical murine tests have shown that dosages are measured in micrograms, not the milligrams with blarcamesine. That's a factor of a thousand less. One-thousand micrograms in a single milligram.
Therefore, Anavex 3-71 has at least two things going for it. It is apparently much better at diffusing into cells. Dosages are much, much lower. Then, at those tiny doses, profound therapeutic outcomes are induced. Lastly, because of the tiny doses, chances for side effects are minimized, if not altogether obviated.
So, no comparison between the Anavex sigma-1 receptor agonists, compared to the others mentioned in the article. Big, powerful Anavex apples, compared to shrinking, moldy oranges.
When clinical results appear from any of the three Anavex trials, it will no longer be accurate or appropriate to lump all sigma-1 receptor agonists together. Clearly, the Anavex molecules will be revealed as a separate, exemplary category — to begin to successfully treat CNS and other diseases.
falconer66a Sunday, 08/16/20 04:17:29 PM
Re: abew4me post# 265574 0
Post # of 265588
Unique, favorable molecular architectures.
Quote:
And the phenomenal biochemistry comes from?
The Anavex sigma-1 receptor agonists, Anavex 2-73 (blarcamesine) and Anavex 3-71, are shaped like none of the other, less favorable sigma-1 receptor agonists (those mentioned in the article).
Understand, small proteins (such as the sigma-1 receptor) are flexible, malleable; able to be re-shaped or re-configured by the interplay of the multiple adhesive forces between the protein and any attached ligands, other properly-fitting molecules (such as those of Anavex).
In cellular biochemistry, shape is everything. When a modulating molecule such as the sigma-1 receptor is bent out of its properly-functioning shape (which apparently can happen with age or genetic factors), chemical reactions controlled or modulated by the molecule don't happen as often or as thoroughly. In the case of neurons with poorly-shaped sigma-1 receptor proteins, various pathologies result (including Alzheimer's, Parkinson's disease dementia, and Rett syndrome). The Anavex molecules bind to the sigma-1 receptor proteins, and thereby re-shape them to full chemical functionality, allowing them to subsequently modulate a variety of ensuing chemical reactions and processes, all of which restore chemical homeostatic processes within the neuron. The neuron is reverted to a more youthful, more fully functional status.
It's the shape. Simply, the Anavex molecules shape things up inside aging or genetically mal-affected neurons.
https://investorshub.advfn.com/boards/read_ms...=157658053
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