title: 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.
authors.affiliation: Drug Safety Research Laboratory, Daiichi Pharmaceutical Co. Ltd., Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimada
authors.forename: Yukari
authors.initials: Y
authors.lastname: Shikanai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shimomura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Harada
authors.forename: Gen
authors.initials: G
authors.lastname: Watanabe
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Taya
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Kato
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Furuhama
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002491:Central Nervous System Agents / Q000633:toxicity*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011760:Pyrrolidinones / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000187:drug effects / Q000473:pathology; D013076:Sperm Count; D013733:Testicular Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
chemical_list: D002491:Central Nervous System Agents; D011760:Pyrrolidinones; C058876:nefiracetam; D013739:Testosterone; D007986:Luteinizing Hormone