AMPA receptor potentiators: application for depression and Parkinson's disease.
Alpha-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 Parkinson's disease.
O'Neill
Michael J
MJ
Eli Lilly & Co. Ltd., Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, UK. Oneill_Michael_J@Lilly.com
Witkin
Jeffrey M
JM
D000818:Animals; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D018091:Receptors, AMPA / Q000819:agonists* / Q000378:metabolism*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D018690:Excitatory Amino Acid Agonists; C434043:LY 392098; D018091:Receptors, AMPA; D013449:Sulfonamides; D013876:Thiophenes