Therapeutic potential of positive AMPA receptor modulators in the treatment of neuropsychiatric disorders

CNS Drugs
Stefano Marenco, Daniel R Weinberger

Abstract

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.

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