Ampakine
Ampakines or AMPAkines are a subgroup of
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.[1]
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
Several other compounds such as
Presently, CX717 is in phase II clinical trials as a possible non-stimulant pharmacotherapy in the treatment of
Mechanism of action
Ampakines work by
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]
Ampakines have been investigated by DARPA for potential use in increasing military effectiveness.[6]
See also
References
- ^ PMID 22886028.
- PMID 15180479.
- ^ "Ampakines Platform Summary Report" (PDF).
- PMID 17119538.
- PMID 17913925.
- ^ Saletan, William (2008-07-16). "Night of the Living Meds: The U.S. military's sleep-reduction program". Slate. Retrieved 2012-04-05.
Further reading
- Staubli, U.; Rogers, G.; Lynch, G. (1994). "Facilitation of glutamate receptors enhances memory". Proc Natl Acad Sci U S A. 91 (2): 777–781. PMID 8290599.
- Staubli, U.; Perez, Y.; Xu, F. B.; Rogers, G.; et al. (1994). "Centrally active modulators of glutamate receptors facilitate the induction of long-term potentiation in vivo". Proc Natl Acad Sci U S A. 91 (23): 11158–11162. PMID 7972026.
- Arai, A.; Lynch G. (1992). "Factors regulating the magnitude of long-term potention induced by theta pattern stimulation". Brain Research. 598 (1–2): 173–184. S2CID 9775469.
- Arai, A.; Silberg, J.; Kessler, M.; Lynch, G. (1995). "Effect of thiocyanate on AMPA receptor mediated responses in excised patches and hippocampal slices". Neuroscience. 66 (4): 815–827. S2CID 41021252.
- Suppiramaniam, V.; Bahr, B. A.; Sinnarajah, S.; Owens, K.; et al. (2001). "Member of the Ampakine class of memory enhancers prolongs the single channel open time of reconstituted AMPA receptors". Synapse. 40 (2): 154–158. S2CID 9705232.
- Porrino, L. J.; Daunais, J. B.; Rogers, G. A.; Hampson, R. E.; et al. (2005). "Facilitation of task performance and removal of the effects of sleep deprivation by an ampakine (CX717) in nonhuman primates". PLOS Biology. 3 (9): e299. PMID 16104830.
- Bast, T.; da Silva, B. M.; Morris, R. G. (2005). "Distinct contributions of hippocampal NMDA and AMPA receptors to encoding and retrieval of one-trial place memory". Journal of Neuroscience. 25 (25): 5845–5856. PMID 15976073.
External links
- Ampakine Article Abstracts
- Recent Article About CX717
- Article on Ampakines with reference to Alzheimers Archived 2015-02-03 at the Wayback Machine
- US Patent 5,650,409
- US Patent 6,030,968
- US Patent 6,730,677
- US Patent 7,307,073
