Improvement of impaired brain monoamine metabolism by the cognition-enhancing agent nefiracetam after microsphere-induced cerebral embolism in rats.

Nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide DM-9384, CAS 77191-36-7), a pyrrolidone (cyclic GABA) derivative, is a newly developed cognition-enhancing (nootropic) agent. In the present study, the effects of nefiracetam on cerebral monoamine metabolism in rats after microsphere-induced cerebral embolism have been examined. For cerebral embolization, microspheres were injected into the left internal carotid artery. Nefiracetam (3, 10 and 30 mg/kg p.o.) was administered daily to the animals for 13 days from the 9th day after the operation. The levels of DA, DOPAC and HVA in the control (embolism-induced, but untreated) group were significantly decreased compared with those of the normal (non-operated) group. In animals treated with nefiracetam (3 mg/kg p.o.), these monoamine levels were higher than controls in the cortex and hippocampus, whereas they were not significantly changed in the striatum. 5-HT contents in the control group significantly decreased from normal levels in the cortex and hippocampus, on which nefiracetam at various doses had no effect. The levels of 5-HIAA in the control group also decreased, which were, however, significantly increased by 3 mg/kg of nefiracetam. The results suggest that nefiracetam has improving actions on the dysfunction of the dopaminergic and serotonergic systems induced by cerebral embolism.