ONCOGENICITY STUDIES OF THE COGNITION-ENHANCING AGENT NEFIRACETAM IN MICE AND RATS

Oncogenicity studies of nefiracetam (N-(2,6-dimethylphenyl) -2-(2-oxo- 1-pyrrolidinyl) acetamide, DM-9384, CAS 77191-36-7), a new cognition-e nhancing agent, were carried out in male and female mice and rats. The compound was administered in diet for 104 weeks at dosage levels of 3 0, 90 and 270 mg/kg/d for mice and of 200, 600 and 1800 ppm for rats. The administration of nefiracetam produced no effects on survival, app earance or behavior. Body weights of the high dose male mice and rats were occasionally significantly decreased when compared to the control s. When calculated on a g/lanimal/d basis, food consumption was someti mes decreased for these male groups. At necropsy, there was no evidenc e of treatment related changes, nor were these seen on histopathologic al examination. All microscopic changes seen in mice and rats were of the usual type commonly occurring in untreated aged B6C3F1 mice and F3 44 rats. In conclusion, the administration of nefiracetam for 24 month s to B6C3F1 mice and F344/ DuCrj rats produced only slight effects on body weight in the high close males with a no-effect level of 90 mg/kg /d for mice or 600 ppm for rats. There was no evidence of an oncogenic effect of nefiracetam.