RespireRx Pharmaceuticals Inc (RSPI)

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Neuro, BTW, Since it was someone from another company who you discussed the calpain topic with, they may not have encountered calpain related activity because all the other (non-Cortex) Ampakine programs out there chiefly use compounds related to cyclothiazide, and as we know from the calpain papers, cyclothiazide doesn't activate calpain activity.

The only compound we know of that activates calpain activity is CX-614, and it's from Cortex's benzamide family (a benzoxazine). While CX-614 and CX-717 act at different sites on the receptor, the two compounds do have the deactivation mechanism in common (unlike cyclothiazide).

However, another angle to consider is that calpain activity is associated with normal LTP / memory formation. Dr. Lynch discussed this in his calpain related paper. Several other research papers have noted that cyclothiazide does not appear to have the same positive effect on LTP that Cortex's benzamides do. So this might be another explanation as to why CX-614 activates calpain while cyclothiazide doesn't -- that the increased calpain activity is brought on primarily by increased LTP activity, and cyclothiazide simply doesn't upregulate LTP very much. If that's the case, then a potent low impact like CX-717 would also be expected to increase calpain activity significantly, just like CX-614 does (since both strongly upregulate LTP). Of course, whether or not this increased calpain activity is detrimental over time, causing histolological cellular changes, is another question.