Investigation of testicular toxicity of nefiracetam, a neurotransmission enhancer, in rats

Abstract Testicular toxicity of nefiracetam ( N -(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide), a neurotransmission enhancer, was investigated in male Slc:SD rats. Nefiracetam was orally administered daily at 1500 mg/kg for 4 weeks, and the animals were killed sequentially during the course of administration to determine testicular histopathological changes and sperm head counts (SHC), and hormonal changes. Retention of step 19 spermatids, sporadic degeneration of pachytene spermatocytes and step 7 spermatids in the stage VII seminiferous tubules, and a decrease in SHC were seen as earliest changes after 1 week of administration. These changes gradually advanced up to atrophy of seminiferous tubules with multinucleated-giant-cell formation after 4-week administration. Serum and testicular testosterone levels were decreased, but recovered to the control levels within a day following a single administration, and the decreases were repeated after 1-week administration. These results suggest that nefiracetam-induced earliest changes could be caused by the decreased level of testicular testosterone.