CELLULAR MECHANISMS UNDERLYING COGNITION-ENHANCING ACTIONS OF NEFIRACETAM (DM-9384)

We have studied cellular mechanisms underlying cognition-enhancing act ions of nefiracetam (DM-9384), a newly developed cognitive enhancer, b y biochemical experiments on cholinergic and GABAergic transmissions a s well as electrophysiological experiments on neuronal Ca2+ channels. In behavioral experiments in rats, nefiracetam (3 mg/kg) ameliorated a mnesia induced by basal forebrain (BF) lesion or treatment of scopolam ine. Biochemical experiments revealed that nefiracetam increased uptak e and release of transmitters in both cholinergic and GABAergic system s in rat brain. In electrophysiological studies, nefiracetam (1 mu M) increased long-lasting (N/L-type) Ca2+ channel currents in NG108-15 ce lls. The nefiracetam action on Ca2+ channels was blocked by pertussis toxin (PTX). The results suggest that nefiracetam improves impaired me mory by facilitating cholinergic and GABAergic transmissions in the br ain. It is further suggested that PTX-sensitive G-proteins and Ca2+ ch annels associated with these G-proteins are responsible for the action of nefiracetam on neurotransmission.