RespireRx Pharmaceuticals Inc (RSPI)

[gfp927z]

If nothing else, that Lifelike Biomatic patent provides a good overview of the various families of compounds out there that have AMPA upmodulating activity -

1) Benzoylpiperidines - CX-516, CX-546 (Cortex)
2) Benzoxazines - CX-614 (Cortex)
3) Benzothiadiazides - Cyclothiadiazide
4) Benzothiadiazines - S-18986 (Servier)
5) Benzoylpyrrolidines - CX-554 (Cortex)
6) Biarylpropylsulfonamides - LY-392098, LY-404187, LY-503430 (Lilly)
7) Pyrrolidinones - Aniracetam, Piracetam
8) Azepines - Benzoxazepines (Organon has some patents on these).

I didn't see Benzofurazans listed (Org-24448), though perhaps these might overlap into one of the above families.

The idea of using an NMDA upmodulator in combination with an AMPA upmodulator could have some merit, though it adds another layer of potential side effects. The NMDA receptor is downstream of the AMPA receptor, so upregulating AMPA already indirectly upregulates NMDA activity. The NMDA receptor can also be stimulated directly via its glycine binding site. A potential advantage of stimulating NMDA activity indirectly via an Ampakine is that by being allosteric at the AMPA receptor, the Ampakine merely magnifies the normal existing neural activity, as opposed to a direct NMDA agonist which initiates new neural activity all by itself.

The idea of actually fusing the functional moiety of an AMPA upmodulator with the functional portion of a NMDA modulator (into a single molecule) is an interesting idea worth getting a broad patent on, but we'll see if anything ever comes of it.