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

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  • Brain distribution of idebenone (CV-2619) and its effect on local cerebral glucose utilization in rats.
  • 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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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.

収録刊行物

  • 日本薬理学雑誌

    日本薬理学雑誌 88 (2), 109-123, 1986

    公益社団法人 日本薬理学会

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