Anavex Life Sciences Corp (AVXL)

[falconer66a]

May Be Related To Rapid, Complete Cellular Absorption

Falconer, so what in your opinion is causing the high doses to produce low blood concentrations?

There could be multitude of explanations for the varying concentrations of Anavex 2-73 in varying individuals and sites in their bodies. The quantitative factors (I believe) are these:

1. Dosage, total milligrams administered each day.

2. Consequent serum (blood) concentrations of absorbed, chemically unaltered drug molecules.

3. Next, concentrations of the drug that cross the blood/brain barrier, thereby floating or dissolved in the fluids surrounding actual nerve cells.

4. Then, the concentrations of the molecule that penetrate or are transported into the cytosol, the liquid environment inside the nerve cells.

5. Lastly, and perhaps most significant are the concentrations of free, chemically unbound drug molecules able to contact and bind to the sigma-1 receptors.

Dosage is easily understood and controlled. No mystery there. (Although optimal dosages for varying body chemistries or genetics may need to be determined, if they can be.)

Plasma concentrations, in blood fluid, should be easy to quantify, using chemical analysis. Draw some blood, and measure. But, as the trial data imply, plasma (blood) concentrations do not always predict or correlate with dosage or treatment efficacy

Most important, and very hard to quantify would be actual concentrations that get inside the neurons themselves, where the drug molecules actually work. Same with trying to quantify concentrations bound to the active sigma-1 receptor sites.

Here’s a hypothesis. Some participants had very low blood concentrations, even with normal or high dosages. How could that be? Might it be this.

For these particular people, the drug molecules easily, quickly and thoroughly pass out of the blood and concentrate in the neurons, where they, in high cellular (but no longer serum) concentrations do their chemical work. The tests measured only blood concentrations. But because so much of the drug ended up quickly inside cells, the serum (blood) concentrations really were low. Most of the drug, undetected, was hidden inside the nerve cells, were in high internal concentrations they did their restorative work.

For some, low serum (blood) concentrations may be strong indications that most of the drug gets quickly and thoroughly inside neurons. Concentrations inside of the cells, may be high, thereby prompting good results, even with tiny concentrations out in the blood.

The blood test may not at all be an accurate measure of the effective concentrations inside the neurons themselves. That’s where the work is done. Blood concentrations may not indicate or predict anything. Anavex 2-73 doesn’t do its chemical magic out in the blood, only inside neurons themselves.