EXAMINATION OF LESIONS IN THE URINARY-BLADDER AND KIDNEY OF DOGS INDUCED BY NEFIRACETAM, A NEW NOOTROPIC AGENT

Toxic lesions induced by nefiracetam, a nootropic drug, in the urinary bladder and kidney were examined by repeated oral administration of 3 00 mg/kg/day for 1, 2, 3, 4, or 11 wk to male and female beagle dogs. Each dog was sacrificed after each treatment period, and urinalysis an d serum biochemistry were performed for surviving dogs at several time points. One male and 2 females died during week 10 or 11. Degeneratio n and desquamation of epithelial cells and edema and hemorrhage in the lamina propria were observed in the urinary bladder after 1 wk of tre atment. These changes became severe as time progressed and were reflec ted in the clinical abnormalities of hematuria and increased protein e xcretion in urine. However, epithelial regeneration and hyperplasia we re seen thereafter, and almost no change was seen in the urinary bladd er after treatment for 11 wk. Instead of recovery as in the urinary bl adder, the kidney showed epithelial degeneration and hyperplasia in th e papilla and collecting duct and interstitial congestion and hemorrha ge after treatment for 11 wk. Extensive hemorrhage and papillary necro sis were seen in animals that died during week 10 or 11 of dosing. The se kidney changes were associated with increased urinary volume and de creased osmotic pressure. The lesions are thought to have a common eti opathogenesis and to be initiated by the epithelial damage with a time lag between expression of injury in the urinary bladder and the kidne y.