Brain distribution of idebenone (CV-2619) and its effect on local cerebral glucose utilization in rats.
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- NAGAI Yasuo
- Central Research Division, Takeda Chemical Industries, Ltd.
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- YOSHIDA Kiyoshi
- Central Research Division, Takeda Chemical Industries, Ltd.
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- NARUMI Shigehiko
- Central Research Division, Takeda Chemical Industries, Ltd.
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- TANAYAMA Shigeharu
- Central Research Division, Takeda Chemical Industries, Ltd.
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- NAGAOKA Akinobu
- Central Research Division, Takeda Chemical Industries, Ltd.
Bibliographic Information
- Other Title
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- イデベノン(CV‐2619)の脳内分布および脳内グルコース利用率に及ぼす影響
- イデベノン CV-2619 ノ ノウナイ ブンプ オヨビ ノウナイ グルコース
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Abstract
To investigate the possible action-sites of a cerebral metabolism activator, idebenone (CV-2619), its distribution in the brain and effect on local cerebral glucose utilization (LCGU) were studied both in normal rats (WKY) and in stroke-prone spontaneously hypertensive rats (SHRSP) with cerebrovascular lesions. At 5 min after intravenous administration of [14C] CV-2619 (10 mg/kg), the distribution ratio in the brain was 0.45 ?? 0.56% of the dosage. Autoradiographic study showed that 14C levels were higher in the white matter than in the grey matter. When [14C] CV-2619 was administered orally (100 mg/kg) and intraperitoneally (30 mg/kg), 14C levels in eleven brain regions (15 min after administration) were 0.22 ?? 0.39 μg/g (CV-2619 equivalent) and 1.11 ?? 1.30 μg/g, respectively, in WKY and 0.17 ?? 0.28 μg/g and 1.66 ?? 1.87 μg/g, respectively, in SHRSP. Total 14C levels were not markedly different among the brain regions of the rats. The analysis of unchanged CV-2619 and its metabolites revealed that unchanged CV-2619 in the cerebral cortex, thalamus and cerebellum was relatively higher than that in the other brain regions. Studies on LCGU demonstrated that CV-2619 (30 mg/kg/day, i.p., for 3 days) improved the decrement of LCGU in the temporal cortex, thalamus dorsomedial nucleus, subthalamic nucleus, mamillary body, hippocampus dentate gyrus, caudate-putamen, inferior colliculus and cerebellar nucleus of SHRSP with stroke. Based on these results, the possible action-sites of CV-2619 for its main pharmacological effects were discussed.
Journal
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- Folia Pharmacologica Japonica
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Folia Pharmacologica Japonica 88 (2), 109-123, 1986
The Japanese Pharmacological Society
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Keywords
Details 詳細情報について
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- CRID
- 1390282679250003840
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- NII Article ID
- 130000759636
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- NII Book ID
- AN00198335
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- COI
- 1:CAS:528:DyaL28XltVOqs7w%3D
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- ISSN
- 13478397
- 00155691
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- NDL BIB ID
- 3099191
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- PubMed
- 3770589
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed