Replies to post #23641 on RespireRx Pharmaceuticals Inc (RSPI)

[enemem]

Everything Varney wrote is reasonable, but he ignores the issue of ampakines promoting wakefulness. If they can balance the respiration-rescuing effect of ampakines with another compound which compensates for ampakines' arousal effects, it could work.

Alternatively, if the effective dosage for SA is lower than the effective dosage for the arousal effects, then there's no problem either. Looking at the sleep deprivation study, ampakines impacted sleepiness at doses as low as 100 mg.

I don't think ampakines will be useful for ALS. My understanding is that motoneurons die from excitotoxic effects secondary to Ca2+ entry -- that's why the only disease-slowing drug currently used (riluzole) is effective, since it reduces Ca2+ entry and persistent Na+ current (both of which increase cell excitability). Ampakines (low-impacts at least) increase excitability. The high-impacts, which upregulate BDNF would be a different story.

If ampakines do anything for ALS, they may maintain good function longer, but accelerate the overall decline.

[gfp927z]

Davidal, Who would have thought 5 years ago that we'd be talking about respiration being a key indication for Ampakines? It's funny how things work out.

Speaking of the 12th cranial nerve, I still remember the old mnemonic device we came up with for remembering the 12 cranial nerves - 'On Old Olympus' Towering Top, A Fat Vested German Vended A Hop'. There were numerous bawdier versions :o)

I also remember the one for the Kreb's cycle - 'All Chemists In the Kremlin Synthesize Foreign Molecules'. To this day I can still diagram the entire Krebs cycle from that jingle, including the ATPs and electrons (Acetyl-CoA, Citrate, Isocitrate, Succinate, alpha-Ketoglutarate, Fumarate, Malate). There was one for Glycolysis also - 'George Gershwin Found Frank Gershwin Playing 4 Piano Pieces'.