Recent advances in positive allosteric modulators of the AMPA receptor.
The alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propioic acid (AMPA) subtype of glutamate receptors mediate fast excitatory neurotransmission throughout the mammalian nervous system and participate in the forms of synaptic plasticity that are considered to underlie learning and memory. Positive allosteric modulators of these receptors are the subject of much investigation because of their emerging therapeutic potential for a range of psychiatric and neurological disorders such as schizophrenia and Alzheimer's disease. This review focuses on the most recent developments in preclinical and clinical research on novel classes of AMPA receptor positive modulators and highlights how the application of biostructural studies has increased our understanding of the biophysical effects produced by these drugs.
Morrow
John A
JA
Department of Molecular Pharmacology Organon Laboratories Ltd., Newhouse, Lanarkshire, UK. j.morrow@organon.co.uk
Maclean
John K F
JK
Jamieson
Craig
C
D000818:Animals; D006801:Humans; D008958:Models, Molecular; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D013329:Structure-Activity Relationship
D018091:Receptors, AMPA