Replies to post #4611 on RespireRx Pharmaceuticals Inc (fka RSPI)

[ggg7ggg]

Wow. Quite a question there Younger Brother! :-)

[gfp927z]

WMG2, Good question. Not being a neurochemist, I'm not sure, but if the bond was irreversible then the Ampakine's effect (inhibiting receptor deactivation and/or desensitization) would presumably never wear off. Since it does wear off, one would have to assume that the bond is reversible.

Another alternative hypothesis would be that even if the Amapkine was irreversibly bound, its effects could wear off via a feedback loop phenomenon, similar to what happens with BDNF upregulation. The problem with that theory is that with all the receptors forever bound up with Ampakine, there would be no new receptors available for the next day's dose to produce their effects, which clearly doesn't jive with reality.

So one would have to conclude that the bond must be reversible. I assume that would make Amakines similar to other small molecule neuro related drugs out there, whose effects wear off after a certain number of hours presumably because the drug dissociates/separates from the receptor site. If Neuro is out there, I'm sure he could better explain how this works.

As we know though, Ampakines do possess the added characteristic of BDNF upregulation (in addition to their direct short term effects on receptor deactivation/desensitization). So even though the Ampakine is no longer present/receptor bound, it continues to have long lasting effects on BDNF production for several days. So any "side effects" related to the presence of the BDNF would
also continue on even though the drug itself is no longer present. Fortunately though, this kind of "side effect" would be the beneficial/desired therapeutic effect of BDNF (neuroprotection, neuroregeneration, neurogenesis, etc).

Addendum - Now you've got me wondering - does a drug's halflife mainly reflect - 1) the time for it to dissociate/separate from the receptor site, 2) the time for it to chemically break down in the bloodsteam and be cleared/metabolized by the body, 3) the time for the receptor to become unresponsive to its effects (feedback loop), or some combination of 1,2,3 ?