Therapeutic potential of positive AMPA receptor modulators in the treatment of neuropsychiatric disorders.
Drugs that potentiate the activity of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor cause a complex cascade of consequences in experimental models, ranging from enhancement of long-term potentiation to induction of neurotrophic factors. Animal studies characterising the pharmacological and behavioural effects of these substances have provided the rationale for several initial attempts to use these drugs in neuropsychiatric clinical settings. Applications in schizophrenia, Alzheimer's disease and mild cognitive impairment have been initiated. Other trials with these compounds include the treatment of Fragile X syndrome, and possible future applications may be in the field of Parkinson's disease. The literature published to date is limited mostly to small phase I or II trials, so there is no conclusive evidence for or against the use of these drugs. Substantial questions remain concerning which compounds to use, in what dose, for what condition and for how long.
Marenco
Stefano
S
Genes, Cognition and Psychosis Program, Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. marencos@mail.nih.gov
Weinberger
Daniel R
DR
D000818:Animals; D001927:Brain Diseases / Q000150:complications / Q000188:drug therapy*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D004195:Disease Models, Animal; D006801:Humans; D001523:Mental Disorders / Q000150:complications / Q000188:drug therapy*; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018091:Receptors, AMPA / Q000819:agonists*
D018697:Nootropic Agents; D018091:Receptors, AMPA