Effects of metrifonate on memory impairment and cholinergic dysfunction in rats

Akio Itoh, Atsumi Nitta, Yuki Katono, Miho Usui, Kazumasa Naruhashi, Ryuichi Iida, Takaaki Hasegawa, Toshitaka Nabeshima

研究成果: Article査読

39 被引用数 (Scopus)

抄録

Metrifonate is an organophosphorous compound that has been used in the treatment of schistosomiasis. In this study, we investigated the effects of metrifonate on the impairment of learning and on central cholinergic dysfunction in scopolamine-treated and basal forebrain-lesioned rats. Oral administration of metrifonate (5.0-15.0 mg/kg) ameliorated the scopolamine- and basal forebrain lesion-induced learning impairment in the water maze and passive avoidance tasks. Metrifonate (50 and 100 mg/kg) also significantly increased extracellular acetylcholine levels but decreased choline levels in the cerebral cortex of the basal forebrain-lesioned rats. The basal forebrain lesion decreased the cholinesterase activity in the cerebral cortex, and metrifonate (100 mg/kg) further reduced the cholinesterase activity. However, cholinesterase inhibition was not observed at the dose that ameliorated learning impairments. These results indicated that metrifonate ameliorated the impairment of learning in both scopolamine-treated and basal forebrain-lesioned rats by not only increasing extracellular acetylcholine levels by inhibiting cholinesterase, but also by undefined other mechanism(s). This finding suggests the usefulness of metrifonate for the therapy of Alzheimer's disease.

本文言語English
ページ(範囲)11-19
ページ数9
ジャーナルEuropean Journal of Pharmacology
322
1
DOI
出版ステータスPublished - 12-03-1997

All Science Journal Classification (ASJC) codes

  • 薬理学

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