There is a consensus that current treatments of
schizophrenia do not offer satisfactory efficacy for negative and
cognitive symptoms. Recently, the dopaminergic hyperfunction hypothesis of
schizophrenia has been enriched by the addition of the glutamatergic hypofunction concept. Accordingly, agents enhancing glutamatergic transmission should provide benefit in
psychosis. In fact, some preclinical studies suggest that positive modulators of alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic
acid (
AMPA) receptors, previously developed mainly for
dementia, may fulfill such expectations. These agents attenuate various biochemical or behavioral effects produced by
amphetamine or
methamphetamine and enhance the action of
antipsychotics. More importantly, preliminary clinical studies with the most advanced member of this class, CX-516(Cortex
Pharmaceuticals Inc), indicate beneficial action on negative and
cognitive symptoms as an add-on treatment t o
clozapine. If these observations are confirmed in a larger scale clinical trial, this approach could be a major improvement in the treatment of
schizophrenia.