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

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Abstract

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.

Original languageEnglish
Pages (from-to)11-19
Number of pages9
JournalEuropean Journal of Pharmacology
Volume322
Issue number1
DOIs
Publication statusPublished - 12-03-1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology

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    Itoh, A., Nitta, A., Katono, Y., Usui, M., Naruhashi, K., Iida, R., Hasegawa, T., & Nabeshima, T. (1997). Effects of metrifonate on memory impairment and cholinergic dysfunction in rats. European Journal of Pharmacology, 322(1), 11-19. https://doi.org/10.1016/S0014-2999(96)00977-6