Brain distribution of idebenone and its effect on local cerebral glucose utilization in rats

To investigate the possible action sites of a cerebral metabolism activator, idebenone, (6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone), its distribution in the brain and effect on local cerebral glucose utilization (LCGU) were studied in normal (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) with cerebrovascular lesions. 14C-Idebenone distributed rapidly into the brain after intravenous administration (10 mg/kg), and the total 14C contents in the brain at peak time corresponded to 0.45-0.56% of the dosages. An autoradiographic study showed that the 14C levels were higher in the white than in the gray matter. When 14C-idebenone was administered orally (100 mg/kg) and intraperitoneally (30 mg/kg), the total 14C levels were not markedly different among the brain regions of the rats. The concentration of unchanged idebenone was higher in the cerebral cortex, thalamus, and cerebellum than that in the other brain regions. Studies on LCGU demonstrated that idebenone (30 mg/kg/day, i.p., for 3 days) improved the reduction of LCGU in SHRSP with stroke, especially in the temporal cortex, thalamus dorsomedial nucleus, subthalamic nucleus, mamillary body, hippocampus dentate gyrus, caudate-putamen, inferior colliculus, and cerebellar nucleus. Based on these results, possible action sites of idebenone for its main pharmacologic effects are discussed.