Nefiracetam enhances acetylcholine outflow from the frontal cortex: in vivo microdialysis study in the rat

The effects of nefiracetam [DM-9384; N-(2, 6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide], a cognitive enhancer, on extracellular acetylcholine and glutamic acid in the frontal cortex were studied using brain microdialysis in freely moving rats. Nefiracetam administration (1 mg/kg, p.o.) doubled the amount of acetylcholine in the dialysate. When tetrodotoxin was added to the perfusion solution, the basal level of acetylcholine decreased and nefiracetam caused no increase in acetylcholine outflow. The amount of glutamic acid in the dialysates was not affected by nefiracetam. These results suggest that nefiracetam increases the amount of acetylcholine within the cholinergic synaptic clefts.