[Effects of idebenone (CV-2619) on neurological deficits, local cerebral blood flow, and energy metabolism in rats with experimental cerebral ischemia].
Improvement of energy metabolism in ischemic cerebral tissue benefits the therapy of occlusive cerebrovascular lesions. In the present study, the effects of 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinone (idebenone, CV-2619) on neurological signs, local cerebral blood flow, and cerebral energy metabolism were assessed in stroke-prone spontaneously hypertensive rats (SHRSP) with bilateral carotid artery occlusion (BCAO). Pretreatment with CV-2619 (10-100 mg/kg, p.o.) for three or ten successive days delayed the onset of ischemic seizure (acute stroke) and prolonged survival time in the SHRSP. When the compound (100 mg/kg, i.p.) was given once 30 min after BCAO, it exerted similar ameliorating effects on the neurological deficits. When CV-2619 (100 mg/kg for 3 days) was given orally, it did not inhibit a decrease in regional cerebral blood flow induced by the carotid artery occlusion. However, the same treatment markedly inhibited increases in lactate content and lactate/pyruvate ratio and a decrease in ATP content in the cerebral cortex. In addition, the compound showed no effect on cerebral blood flow in normal rats. These results suggest that CV-2619 has an ameliorating effect on neurological deficits related with cerebral ischemia, and this effect is mediated by improved cerebral energy metabolism.
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D016227:Benzoquinones; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D002540:Cerebral Cortex / Q000032:analysis; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D007773:Lactates / Q000032:analysis; D019344:Lactic Acid; D008297:Male; D011809:Quinones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D014451:Ubiquinone / Q000031:analogs & derivatives
D016227:Benzoquinones; D007773:Lactates; D011809:Quinones; D014451:Ubiquinone; D019344:Lactic Acid; D000255:Adenosine Triphosphate; C036619:idebenone