(for example, does not potentiate AMPA as aniracetam does).
about aniracetam and AMPA, i found this over at the newsgroups.
"Ampakines, like aniracetam, amplify neuronal signaling by stimulating,
and thereby enhancing the receptiveness of AMPA receptors to
glutamate. AMPA receptors, including the other chief glumate
receptor, namely NMDA, are implicated in many actions in the central
nervous system - such as excitotoxicity.
Excessive glutamate activity is conducive to excitotoxicity and
consequently neuronal death. Excitotoxicity is most likely to arise
in young individuals, whose glutamate receptors are healthy and
responsive."
any comments?
It's a lot more complicated than that. Here is the simplified version, the article coming out soon goes into a lot more detail:
1. Aniracetam does not directly stimulate AMPA receptors - instead, it slows the rate of desensitization/deactivation in the presence of an agonist, thus amplifying long-term potentiation. It does this allosterically, in other words, it does not directly act at the binding site. It only has an effect in the presence of an agonist. So you can't really compare it to an excitotoxin.
2. Aniracetam is selective at certain types of AMPA receptors, in certain areas of the brain.
3. Aniracetam-induced AMPA receptor activation --> kainate receptor desensitization, serving as a negative feedback mechanism. It is possible that this actually leads to a net reduction of excitotoxicity, since, as mentioned previously, aniracetam does not act as an agonist.
4. One of the metabolites of aniracetam positively modulates group II metabotropic glutamate receptors, and some subtypes of mGlu reduce excitotoxicity.
5. The metabolites of aniracetam have many other effects that could potentially counteract any possible excitotoxicity. Accordingly, the majority of the research shows aniracetam to prevent excitotoxicity. Instead of theories, we actually have information on the endpoint, which on balance is in favor of aniracetam acting as a neuroprotectant.
Also, the contention that excitotoxicity is more likely to occur in young individuals is completely wrong, given that younger individuals have much more going for them in terms of natural defense mechanisms, and older brain cells are more susceptible to injury. This is why neurodegeneration happens relatively quickly, instead of gradually throughout life.