Name:	CX516
Other Names:	Ampalex
Therapeutic Applications:	cognition/memory enhancement
Therapy Types:	pharmacological
Mechanisms:	AMPAkines
Development Status:	investigational in U.S.
FDA Phase:	Discontinued
Primary Medical Role:	Improve cognitive function in patients with mild-to- moderate Alzheimer's disease.
Role in Alzheimer's Disease:	May improve cognitive function in AD patients by pharmacologically stimulate AMPA receptor-mediated synaptic responses. Reported to enhance memory performance in healthy elderly subjects.
Pharmacological Role:	1-(quinoxalin-6-ylcarbonyl) piperidine, a novel AMPA receptor mediator, it facilitates the function of a subtype of glutamate receptor by increasing the amount of current flow that takes place when glutamate binds to the receptor. It is also used for treatment of Schizophrenia.
Companies:	Cortex Pharmaceuticals, Inc.
Notes:	ClinicalTrials.gov NCT00001662 was completed. This record updated Dec 10, 2008.

References

Arai AC, Xia YF, Rogers G, Lynch G, Kessler M. Benzamide- type AMPA receptor modulators form two subfamilies with distinct modes of action. J Pharmacol Exp Ther. 2002 Dec ;303(3):1075-85. Abstract

Ikonomovic MD, Mizukami K, Warde D, Sheffield R, Hamilton R, Wenthold RJ, Armstrong DM. Distribution of glutamate receptor subunit NMDAR1 in the hippocampus of normal elderly and patients with Alzheimer's disease. Exp Neurol. 1999 Nov;160(1):194-204. Abstract

Yamada KA. Modulating excitatory synaptic neurotransmission: potential treatment for neurological disease? Neurobiol Dis. 1998 Aug;5(2):67-80. Abstract

Lynch G. Memory and the brain: unexpected chemistries and a new pharmacology. Neurobiol Learn Mem. 1998 Jul-Sep;70(1- 2):82-100. Abstract

Hampson RE, Rogers G, Lynch G, Deadwyler SA. Facilitative effects of the ampakine CX516 on short-term memory in rats: correlations with hippocampal neuronal activity. J Neurosci. 1998 Apr 1;18(7):2748-63. Abstract

Ingvar M, Ambros-Ingerson J, Davis M, Granger R, Kessler M, Rogers GA, Schehr RS, Lynch G. Enhancement by an ampakine of memory encoding in humans. Exp Neurol. 1997 Aug;146(2):553-9. Abstract

Lynch G, Granger R, Ambros-Ingerson J, Davis CM, Kessler M, Schehr R. Evidence that a positive modulator of AMPA- type glutamate receptors improves delayed recall in aged humans. Exp Neurol. 1997 May;145(1):89-92. Abstract

Arai A, Kessler M, Ambros-Ingerson J, Quan A, Yigiter E, Rogers G, Lynch G. Effects of a centrally active benzoylpyrrolidine drug on AMPA receptor kinetics. Neuroscience. 1996 Nov;75(2):573-85. Abstract

Arai A, Kessler M, Rogers G, Lynch G. Effects of a memory- enhancing drug on DL-alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptor currents and synaptic transmission in hippocampus. J Pharmacol Exp Ther. 1996 Aug;278(2):627-38. Abstract

Gu JG, Albuquerque C, Lee CJ, MacDermott AB. Synaptic strengthening through activation of Ca2+-permeable AMPA receptors. Nature. 1996 Jun 27;381(6585):793-6. Abstract

Lynch G, Kessler M, Rogers G, Ambros-Ingerson J, Granger R, Schehr RS. Psychological effects of a drug that facilitates brain AMPA receptors. Int Clin Psychopharmacol. 1996 Mar;11(1):13-9. Abstract

Staubli U, Rogers G, Lynch G.Facilitation of glutamate receptors enhances memory. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):777-81. Abstract