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Recent Advances in the Discovery of Selective AMPA Receptor Positive Allosteric Modulators

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This article highlights recent advances in the discovery of new positive allosteric modulators of the AMPA receptor, excluding compounds of thiadiazine chemotype, most of which were developed by Servier and the University of Liege. The field of AMPA receptor modulators continues to be a fertile area for the discovery of new potential therapeutic agents, and recent years have seen a marked diversification in the range of chemotypes prepared. An overview is also given of the recent key new biological data.

Keywords: AMPA positive modulator; AMPA receptor; AMPAR complex; Cyclopropane Derivatives; D-amphetamine-stimulated locomotion; FLIPR-based assays; FLUO-4; HEK293; Iminothiazole; Parkinson's disease; Phenethyl Sulfonamide Series; Pyrrole/Thiophene Acid Series; Trifluoromethylpyrazole; Trifluoromethylpyrazole Series; aromatic thiophene linker; benzothiadiazines; cell voltage-clamp electrophysiology; chemotypes; cognitive performance; cornichon proteins; cystine-knot AMPAR; deactivation kinetics; glutamate bound dimer; glutamatergic neurotransmitter system; indane core structure; neurodegenerative diseases; postsynaptic membrane; preclinical behavioural testing; schizophrenia,Alzheimer's disease; synaptic plasticity; tetrameric complex; thiadiazine chemotype; trifluoromethylpyrazole

Document Type: Research Article


Affiliations: Neurosciences CEDD, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow,Essex, CM19 5AW, UK.

Publication date: 2010-10-01

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