AMPA receptors only exist within the CNS, in fact within specific regions of the brain and spinal cord, so while an artifact(or toxicity) could occur outside of the CNS, one would expect an artifact, or toxicity, to occur within the brain since the dynamic of Ampakine/AMPA receptor interaction occurs within specific regions of the brain.
The dosage thing: the fact that an artifact occurs at a set dosage doesn't bother me. One would expect a threshold effect for an artifact(or for that matter toxicity) to occur. One needs a certain amount of substrate for a toxic reaction(or artifact to occur). Recall, CX717 is injected into the animals, then cross the Blood Brain Barrier and then interact with AMPA receptors.
There are lines of evidence that are neutral for either toxicity or artifact as defined above: threshold dosage, target organ, and other lines of evidence strongly supporting artifact after cell death: lack of any behavior change, lack of abnormality on fresh frozen microscopy, lack of any progression with continued heroic dosing. There is, however, a strong basis for belief that the cells in question are healthy before death. That would appear to be the crux of the matter. If Cortex can consistently demonstrate that immediate frozen cells are healthy, no behavioral changes, artifact seen with traditional fixation . . . they have a good basis for liberalization to proceed with phase IIb.
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