AMPA receptor potentiators as novel antidepressants.

Depression affects a large percentage of the general population and can produce devastating consequences to affected individuals, families and society. Although the treatment of depression has been advanced by traditional antidepressants, improvements are needed across several dimensions (e.g., overall treatment efficacy, therapeutic onset time, and side effect profile). The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor has an allosteric modulatory site(s) for which potent positive modulators (potentiators) have been designed. These compounds produce antidepressant-like effects in animal models, increase levels of brain-derived neurotrophic factor (BDNF) and engender neurogenesis in vivo. Although these effects are also produced by traditional antidepressants, AMPA receptor potentiators appear to produce their effects through a novel mechanism.