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Ampakine
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AMPA
Ampakines are a class of compounds known to enhance attention span and alertness, and facilitate learning and memory. The ampakines take their name from the glutamatergic AMPA receptor with which they strongly interact. The AMPA receptor, in turn, gets its name from AMPA, which selectively binds to it.
Ampakines have been investigated by DARPA for potential use in increasing military effectiveness.[1]
Contents
[hide] 1 Effects
2 Examples and structure 2.1 Racetam family
2.2 Cortex Pharmaceuticals
2.3 Eli Lilly/other
3 Mechanism
4 Side effects
5 Uses
6 References
7 Further reading
8 External links
[edit] Effects
Unlike earlier stimulants (e.g. caffeine, methylphenidate (Ritalin), and the amphetamines), ampakines do not seem to have unpleasant, long-lasting side effects such as sleeplessness.
They are currently being investigated as potential treatment for a range of conditions involving mental disability and disturbances such as Alzheimer's disease, Parkinson's disease, schizophrenia, treatment-resistant depression (TRD) or neurological disorders such as Attention Deficit Hyperactivity Disorder (ADHD), among others.
Ampakine activity has been established as one of the modes of action of the well established class of nootropics, the racetam drugs such as piracetam, aniracetam, oxiracetam and pramiracetam, however these drugs have multiple modes of action and produce only weak AMPA receptor activation, and it is unclear how significant their ampakine actions are in producing their nootropic effects. More recently developed ampakine compounds are much more potent and selective for the AMPA receptor target, and while none of the newer selective ampakine compounds have yet come onto the market, one compound CX717 is currently in Phase II clinical trials as of 2008.
[edit] Examples and structure
Four structural classes of ampakine drugs have been developed so far:[2]
the pyrrolidine derivative racetam drugs such as piracetam and aniracetam
the CX- series of drugs which encompass a range of benzoylpiperidine and benzoylpyrrolidine structures
benzothiazide derivatives such as cyclothiazide and IDRA-21
biarylpropylsulfonamides such as LY-392,098, LY-404,187, LY-451,646 and LY-503,430
[edit] Racetam family
The parent compound in which the AMPA modulating activity was first characterised was the well known nootropic drug aniracetam. Several drugs in the racetam family have been reported as producing ampakine effects, but while this has been well established for some compounds such as aniracetam and pramiracetam, it is unclear if all of the racetam family act in this way, as the racetam drugs appear to have multiple modes of action.
[edit] Cortex Pharmaceuticals
Cortex Pharmaceutical AMPAkines CX-546, CX-516, and CX-614
Since the discovery of the ampakine mode of action as one of the means by which the racetams produce their nootropic effects, a wide range of more selective ampakine drugs have been developed by Cortex Pharmaceuticals, who hold patents covering most medical uses of this class of drugs. The best known compounds that have come out of the Cortex drug development program are CX-516 (Ampalex), CX-546, CX-614, CX-691 (Farampator) and CX-717. Org 26576 was invented by Cortex but then licensed to Organon for development.
Several other compounds such as CX-701, CX-1739, CX-1763 and CX-1837 have also been announced as being under current investigation, and while little information has yet been released about them, CX-1739 is believed to be the most potent compound in this class to date, reportedly some 5x the potency of CX-717.
[edit] Eli Lilly/other
Other compounds producing the ampakine activity profile such as IDRA-21 and Eli Lilly's LY-503,430 have been developed by other pharmaceutical companies, but these are only used in animal research at present, and Cortex is the only company currently developing selective ampakine drugs for human use, in partnership with the larger pharmaceutical company Schering-Plough.
[edit] Mechanism
Their action is theorized to be due to facilitation of transmission at cortical synapses that use glutamate as neurotransmitter.[3] This in turn may promote plasticity at the synapse, which could translate into better cognitive performance.[citation needed]
Ampakines work by allosterically binding to particular receptors in the brain, called AMPA-type glutamate receptors. This boosts the activity of glutamate, a neurotransmitter, and makes it easier to encode memory and to learn. In addition, some members of the Ampakine family of drugs may also increase levels of trophic factors such as Brain-derived neurotrophic factor (BDNF).
[edit] Side effects
Few side effects have been determined, but an ampakine called farampator (CX-691) has side effects including headache, somnolence, nausea, and impaired episodic memory.[3]
Subject: A drug for concentration 
Fri Mar 15, 2013 3:34 pm
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