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 language | English |
|---|---|
| Pages (from-to) | 11-19 |
| Number of pages | 9 |
| Journal | European Journal of Pharmacology |
| Volume | 322 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 12-03-1997 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
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Effects of metrifonate on memory impairment and cholinergic dysfunction in rats. / Itoh, Akio; Nitta, Atsumi; Katono, Yuki; Usui, Miho; Naruhashi, Kazumasa; Iida, Ryuichi; Hasegawa, Takaaki; Nabeshima, Toshitaka.
In: European Journal of Pharmacology, Vol. 322, No. 1, 12.03.1997, p. 11-19.Research output: Contribution to journal › Article
TY - JOUR
T1 - Effects of metrifonate on memory impairment and cholinergic dysfunction in rats
AU - Itoh, Akio
AU - Nitta, Atsumi
AU - Katono, Yuki
AU - Usui, Miho
AU - Naruhashi, Kazumasa
AU - Iida, Ryuichi
AU - Hasegawa, Takaaki
AU - Nabeshima, Toshitaka
PY - 1997/3/12
Y1 - 1997/3/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0030931020&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030931020&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(96)00977-6
DO - 10.1016/S0014-2999(96)00977-6
M3 - Article
C2 - 9088864
AN - SCOPUS:0030931020
VL - 322
SP - 11
EP - 19
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -