Positive modulators of the AMPA receptor

Alterations in the excitatory neurotransmission by AMPA-type (alpha-methyl3-hydroxy-5-methyl-4-isoxazol-4-ylpropionic acid) glutamate receptors may be involved in the aetiology of neurological diseases such as Alzheimer's disease and schizophrenia. The potentiation of AMPA-receptor mediated synaptic transmission by allosteric positive modulators of this receptor (Ampakines(TM)) may have beneficial behavioural effects in these diseases. The development of compounds acting as Ampakines has led to CX516 (Ampalex(TM), Cortex Pharmaceuticals), which has reached the early stage of clinical trials for schizophrenia. The number of structural classes of compounds reported in the patent literature as positive modulators of the AMPA receptor is expanding from the earlier benzoyl piperidine (aniracetam) and thiazide (cyclothiazide, diazoxide) chemical series. This review covers the patent literature from the last five years (January 1995 to June 2000) in which there are claims for positive modulators of the AMPA receptor.