Ampakine

Image:cortex pharm AMPAkines.svg, CX-516, and CX-614.]]

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.{{cite web|title=Ampakines Platform Summary Report|url=http://respirerx.com/wp-content/uploads/2017/07/Ampakines-Platform-Summary-Final.pdf}} 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.

Ampakines work by allosterically binding to a type of ionotropic glutamate receptor, called AMPA receptors.

The ampakines are mostly low-impact AMPAR PAMs, though with some exceptions, such as tulrampator (S-47445, CX-1632).

Few side effects have been determined, but an ampakine called farampator (CX-691) has side effects including headache, drowsiness, nausea, and impaired episodic memory.{{ cite journal | display-authors = 4| author = Wezenberg, E.| author2 = Verkes, R. J.| author3 = Ruigt, G. S.| author4 = Hulstijn, W.| author5 = Sabbe, B. G. | title = Acute Effects of the Ampakine Farampator on Memory and Information Processing in Healthy Elderly Volunteers | journal = Neuropsychopharmacology | date = 2007 | volume = 32 | issue = 6 | pages = 1272–1283 | pmid = 17119538 | doi = 10.1038/sj.npp.1301257 | doi-access = free }}

An ampakine called CX456 has been proposed as a treatment for Rett syndrome, after favorable testing in an animal model.{{ cite journal | display-authors = 4| author = Ogier, M.| author2 = Wang, H.| author3 = Hong, E.| author4 = Wang, Q.| author5 = Greenberg, M. E.| author6 = Katz, D. M. | title = Brain-derived Neurotrophic Factor Expression and Respiratory Function Improve after Ampakine Treatment in a Mouse Model of Rett Syndrome | journal = Journal of Neuroscience | date = 2007 | volume = 27 | issue = 40 | pages = 10912–10917 | pmid = 17913925 | pmc = 6672830| doi = 10.1523/JNEUROSCI.1869-07.2007 }}

Ampakines have been investigated by DARPA to treat sleep deprivation-induced cognitive decline.{{cite web | url = http://www.slate.com/id/2195466/ | title = Night of the Living Meds: The U.S. military's sleep-reduction program |last=Saletan|first=William|author-link=William Saletan |magazine=Slate | date = 2008-07-16 | access-date = 2012-04-05 }}

• List of investigational antidepressants

{{Reflist|2}}

• {{ cite journal | author = Staubli, U.| author2 = Rogers, G.| author3 = Lynch, G. | title = Facilitation of glutamate receptors enhances memory | journal = Proc Natl Acad Sci U S A | date = 1994 | volume = 91 | issue = 2 | pages = 777–781 | doi = 10.1073/pnas.91.2.777 | pmid = 8290599 | pmc = 43032 | bibcode = 1994PNAS...91..777S| doi-access = free}}
• {{ cite journal | display-authors = 4| author = Staubli, U.| author2 = Perez, Y.| author3 = Xu, F. B.| author4 = Rogers, G.| author5 = Ingvar, M.| author6 = Stone-Elander, S.| author7 = Lynch, G. | title = Centrally active modulators of glutamate receptors facilitate the induction of long-term potentiation in vivo | journal = Proc Natl Acad Sci U S A | date = 1994 | volume = 91 | issue = 23 | pages = 11158–11162 | pmid = 7972026 | pmc = 45186 | doi=10.1073/pnas.91.23.11158| bibcode = 1994PNAS...9111158S| doi-access = free}}
• {{ cite journal | author = Arai, A.| author2 = Lynch G. | date = 1992 | title = Factors regulating the magnitude of long-term potention induced by theta pattern stimulation | journal = Brain Research | volume = 598 | issue = 1–2 | pages = 173–184 | doi = 10.1016/0006-8993(92)90181-8 | pmid = 1486479 | s2cid = 9775469 }}
• {{ cite journal | author = Arai, A.| author2 = Silberg, J.| author3 = Kessler, M.| author4 = Lynch, G. | date = 1995 | title = Effect of thiocyanate on AMPA receptor mediated responses in excised patches and hippocampal slices | journal = Neuroscience | volume = 66 | issue = 4 | pages = 815–827 | doi = 10.1016/0306-4522(94)00616-D | pmid = 7544449 | s2cid = 41021252}}
• {{ cite journal | display-authors = 4| author = Suppiramaniam, V.| author2 = Bahr, B. A.| author3 = Sinnarajah, S.| author4 = Owens, K.| author5 = Rogers, G.| author6 = Yilma, S.| author7 = Vodyanoy, V. | date = 2001 | title = Member of the Ampakine class of memory enhancers prolongs the single channel open time of reconstituted AMPA receptors | journal = Synapse | volume = 40 | issue = 2 | pages = 154–158 | doi = 10.1002/syn.1037 | pmid = 11252027 | s2cid = 9705232}}
• {{ cite journal | display-authors = 4| author = Porrino, L. J.| author2 = Daunais, J. B.| author3 = Rogers, G. A.| author4 = Hampson, R. E.| author5 = Deadwyler, S. A. | date = 2005 | title = Facilitation of task performance and removal of the effects of sleep deprivation by an ampakine (CX717) in nonhuman primates | journal = PLOS Biology | volume = 3 | issue = 9 | pages = e299 | doi = 10.1371/journal.pbio.0030299 | pmid = 16104830 | pmc = 1188239 | doi-access = free}}
• {{ cite journal | author = Bast, T.| author2 = da Silva, B. M.| author3 = Morris, R. G. | title = Distinct contributions of hippocampal NMDA and AMPA receptors to encoding and retrieval of one-trial place memory | journal = Journal of Neuroscience | date = 2005 | volume = 25 | issue = 25 | pages = 5845–5856 | doi = 10.1523/JNEUROSCI.0698-05.2005 | pmid = 15976073 | pmc = 6724786}}

• [http://www.neurotransmitter.net/ampakines.html Ampakine Article Abstracts]
• [https://www.newscientist.com/article.ns?id=dn7342 Recent Article About CX717]
• [http://www.alzheimersscreen.com/Ampakines.htm Article on Ampakines with reference to Alzheimers] {{Webarchive|url=https://web.archive.org/web/20150203064925/http://www.alzheimersscreen.com/Ampakines.htm |date=2015-02-03 }}
• [https://patents.google.com/patent/US5650409 US Patent 5,650,409]
• [https://patents.google.com/patent/US6030968 US Patent 6,030,968]
• [https://patents.google.com/patent/US6730677 US Patent 6,730,677]
• [https://patents.google.com/patent/US7307073 US Patent 7,307,073]

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{{Ionotropic glutamate receptor modulators}}

Category:AMPA receptor positive allosteric modulators