Glutamate-based therapeutic approaches: ampakines.
Ampakines are a structurally diverse family of small molecules that positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors, and thereby enhance fast, excitatory transmission throughout the brain. Surprisingly, ampakines have discrete effects on brain activity and behavior. Because their excitatory synaptic targets mediate communication between cortical regions, serve as sites of memory encoding, and regulate the production of growth factors, ampakines have a broad range of potential therapeutic applications. Several of these possibilities have been tested with positive results in preclinical models; preliminary clinical work has also been encouraging.
Lynch
Gary
G
University of California, Department of Psychiatry and Human Behavior, Irvine, California 92617, USA. glynch@uci.edu
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008568:Memory / Q000187:drug effects; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D010078:Oxazines / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011487:Protein Conformation; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism
C443080:1-(1,4-benzodioxan-6-ylcarbonyl)piperidine; C097396:1-(quinoxalin-6-ylcarbonyl)piperidine; D004149:Dioxoles; D018690:Excitatory Amino Acid Agonists; D009414:Nerve Growth Factors; D010078:Oxazines; D010880:Piperidines; D018091:Receptors, AMPA; C414782:2H,3H,6aH-pyrrolidino(2'',1''-3',2')1,3-oxazino(6',5'-5,4)benzo(e)1, 4-dioxan-10-one