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, various ampakines are in clinical trials.[1]
Development
A wide range of ampakines have been developed by
RespireRx, which hold patents covering most medical uses of this class of drugs. The best known compounds that have come out of the RespireRx drug development program are
CX-516 (Ampalex),
CX-546,
CX-614,
CX-691 (farampator), and
CX-717.
ORG-26576 was developed by RespireRx 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.
Presently, CX717 is in phase II clinical trials as a possible non-stimulant pharmacotherapy in the treatment of
ADHD.[3] As the AMPA receptors also mediate respiratory drive, CX717 is also being investigated as a therapy in opioid-induced respiratory depression and
spinal-cord injury.
The ampakines are mostly low-impact AMPAR PAMs, though with some exceptions, such as
tulrampator (S-47445, CX-1632).
Side effects
Few side effects have been determined, but an ampakine called
farampator (CX-691) has side effects including headache, drowsiness, nausea, and impaired
episodic memory.[4]
Medical applications
An ampakine called CX456 has been proposed as a treatment for
Rett syndrome, after favorable testing in an animal model.[5]
^
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