Modulating AMPA Receptors for the Treatment of CNS Disorders

Glutamate receptors and the associated neurotransmission have been of interest to the pharmaceutical research community for many years since dysfunction of the glutamatergic signaling pathway has been associated with the pathophysiology of several psychiatric and neurological disorders. The research on ligands modulating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), one subtype of glutamate ionotropic receptor, offers opportunities to modulate fast excitatory synaptic transmission, and to identify new potential therapeutic agents for a range of neurodisease, such as schizophrenia and epilepsy. The field of AMPAR ligands continues to be a dynamic area of drug discovery, with a pronounced diversification of the chemotypes explored as positive allosteric modulators in recent years. This article reviews literature published in this area in the last decade.