RespireRx Pharmaceuticals Inc (RSPI)

[enemem]

GFP, the fact that ampakines have no effect on breathing under baseline conditions is irrelevant: during normal breathing, AMPA receptor activation is saturating, so you have a ceiling effect. What is at issue is whether these compounds reverse opiate-induced respiratory depression: under these conditions, AMPAergic drive to PBC neurons is shunted by mu-opiate receptor activation, and the ampakine-induced upregulation of AMPAergic transmission could bring AMPAergic drive back closer to baseline.

Because brainstem respiratory networks are highly conserved across the mammalian lineage, and because the brainstem is the "oldest" part of the brain, what we know about the system would suggest that pharmacological effects on autonomic breathing in rodents should be replicated in humans. It doesn't mean we aren't all in for a big surprise, but based on what's known, it looks more reasonable than to assume the contrary.

Further, the effect of ampakines on RD is a direct effect on a rather narrow pharmacological perturbation. The other disease states you mention (AD, ADHD)and sleep are much more complicated processes, in which the effects of ampakines are more difficult to foresee. So here again, I find it hard to argue that success with RD has a lower probability of success than in these other cases, since we have so little understanding of its mechanism of efficacy in the indications you mentioned.

All in all, I'm cautiously optimistic. I may be way off base in my interpretation of the literature, but at least there is a basis for forming an opinion. I am much more skittish about regulatory binary events, where the process is completely opaque, and where there are plenty of reasons to be suspicious about the process.