Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

Back

AMPA Receptor Potentiators: Application for Depression and Parkinsons Disease

Author(s): Michael J. O'Neill and Jeffrey M. Witkin

Affiliation: Eli Lilly&Co. Ltd., Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey GU20 6PH, U.K.

Keywords: AMPA receptor potentiator, glutamate, LY392098, LY404187, LY503430, BDNF, Depression, Parkinson's disease

Abstract:

α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors mediate most of the excitatory neurotransmission and play a key role in synaptic plasticity in the mammalian central nervous system (CNS). In recent years several classes of AMPA receptor potentiators have been reported in the literature, including pyrrolidones (piracetam, aniracetam), benzothiazides (cyclothiazide), benzylpiperidines (CX-516, CX-546) and biarylpropylsulfonamides (LY392098, LY404187, LY450108, LY451395 and LY503430). Clinical and preclinical data have suggested that positive modulation of AMPA receptors may be therapeutically effective in the treatment of cognitive deficits. However, recent evidence has shown that in addition to modulating fast synaptic plasticity and memory processes, AMPA receptor potentiators alter downstream signalling pathways and may thereby have utility in other CNS disorders. The present review summarises studies into the effects of AMPA receptor potentiators (with a focus on the biarylpropylsulfonamides) in rodent models of depression and Parkinsons disease.

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

VOLUME: 8
ISSUE: 5
Page: [603 - 620]
Pages: 18
DOI: 10.2174/138945007780618517