Ampakiny

Unlike well-known stimulants ( caffeine , methylphenidate (Ritalin), amphetamines ), ampakinas do not increase blood pressure or pulse rate , do not cause such unpleasant long-term side effects as insomnia , do not cause drug dependence .

Now they are actively investigated as a potential cure for brain diseases such as Alzheimer's disease , Parkinson's disease , schizophrenia and neurological disorders. Ampakins are considered by DARPA as a possible means of increasing the effectiveness of the military ^[1] .

Ampakin activity was established as one of the modes of action of a well-known group of nootropic drugs, racetam . However, these substances have other modes of action and produce a rather weak activating effect on AMPA receptors, and it is not known how strongly their ampakin activity is responsible for their nootropic effects.

After the discovery of the ampakin mechanism, drugs with a stronger and more directed action were developed, most of which are patented by Cortex Pharmaceuticals ( CX-516 ( Ampalex ), CX-546 , CX-614 , CX-691 ( Farampator ), CX-717 ) . None of the substances has yet been released to the market (as of 2008, CX-717 is undergoing clinical trials).

Some pharmaceutical companies are also developing drugs with ampakin activity ( LY-404,187 and LY-503,430 of the company Eli Lilly and Company , IDRA-21 , PEPA , Sunifiram and Unifiram ). However, at the moment they are used only for animal studies, and Cortex Pharmaceuticals (in partnership with the larger company Schering-Plow) is currently the only one developing ampakins for use as drugs.

So far there are not many of them, but ampakin “farampator” (CX-691) exhibits side effects such as headache, drowsiness, nausea, disturbance of temporary (episodic) memory ^[2] .

• Raevsky K.S., Eremin K.O. Allosteric modulators of the glutamate receptor AMPA subtype - a new class of physiologically active substances. // Biomed. chemistry. - 2004. - V. 50, № 6. - p. 523-538. essay

• Staubli U, Rogers G, Lynch G. Related Articles, Facilitation of glutamate receptors enhances memory. Proc Natl Acad Sci US A. 1994 Jan 18; 91 (2): 777-81. PMID 8290599

• Staubli U, Perez Y, Xu FB, Rogers G, Ingvar M, Stone-Elander S, Lynch G. Centrally active modulators of glutamate receptors in vivo. Proc Natl Acad Sci US A. 1994 Nov 8; 91 (23): 11158-62. PMID 7972026

• Arai A, Lynch G. 1992. Factors regulating the magnitude of the long-term potency induced by theta pattern stimulation. Brain Res 598: 173-184. PMID 1486479

• Arai A, Silberg J, Kessler M, Lynch G. 1995. Thiocyanate on the AMPA receptor mediated responses and hippocampal slices. Neuroscience 66: 815-827. PMID 7544449

• Suppiramaniam V, Bahr BA, Sinnarajah S, Owens K, Rogers G, Yilma S, Vodyanoy V. 2001. AMPA receptors. Synapse. 40 (2): 154-8. PMID 11252027

• Porrino LJ, Daunais JB, Rogers GA, Hampson RE, Deadwyler SA (2005) (CX717) in nonhuman primates. PLoS Biol 3 (9): e299. PMID 16104830

• Bast T, da Silva BM, Morris RG. NMDA and AMPA receptors for encoding and retrieval of one-point place memory. J Neurosci. 2005 Jun 22; 25 (25): 5845-56. PMID 15976073

• Ampakine Article Abstracts

• US Patent 5,650,409
• US Patent 6,030,968
• US Patent 6,730,677
• US Patent 7,307,073

• Note on the CX717 in New Scientist (English)
• About the use of ampakinov for the treatment of Alzheimer's disease (English)
• We break wetware ( part 2 ) - the mechanism of action of AMPA-stimulants from a practical point of view ( hacker's view)