In search of novel AMPA potentiators.
Glutamate is the major excitatory neurotransmitter in the brain. Amongst ionotropic receptors responding to glutamate, the AMPA subtype has been considered as essential for the fast excitatory neurotransmission in the central nervous system and the expression and maintenance of long-term potentiation. As glutamate is known to be involved in many neurological and psychiatric disorders, AMPA receptors seem to represent interesting targets to develop therapeutic drugs. Hence, the enhancement of AMPA signals is an approach currently investigated for the management of Alzheimer's disease, schizophrenia or mood disorders. In particular, many efforts are being conducted in the development of AMPA positive allosteric modulators ("potentiators"), which alter the rate of receptor desensitization. The major chemical families developed as AMPA potentiators are aniracetam derivatives, cyclothiazide derivatives and biarylpropylsulfonamides derivatives.
Francotte
Pierre
P
Drug Research Center, Department of Medicinal Chemistry, University of Liège, Av. de l'Hôpital, 1 (B36), 4000 Liège, Belgium. Pierre.Francotte@ulg.ac.be
de Tullio
Pascal
P
Fraikin
Pierre
P
Counerotte
Stéphane
S
Goffin
Eric
E
Pirotte
Bernard
B
D000494:Allosteric Regulation; D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D006801:Humans; D019964:Mood Disorders / Q000188:drug therapy; D011760:Pyrrolidinones / Q000494:pharmacology; D018091:Receptors, AMPA / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology
D001581:Benzothiadiazines; D011760:Pyrrolidinones; D018091:Receptors, AMPA; D013449:Sulfonamides; C036466:aniracetam