title: [Beneficial effects of the combination of idebenone and manidipine 2HCl on neurological deficits and histological changes following cerebrovascular lesions in stroke-prone spontaneously hypertensive rats].
abstract: We investigated the effects of the combination of idebenone, an energy metabolism enhancer, and manidipine 2HCl, a dihydropyridine-derivative calcium antagonist, on neurological deficits and histological changes in the brain and kidneys of stroke-prone spontaneously hypertensive rats (SHRSP) with cerebrovascular lesions (stroke). The SHRSP were kept on a 1% NaCl solution as their drinking water to synchronize the onset of stroke. After the onset of stroke symptoms, the salt solution was replaced with tap water. On the day following the onset of stroke, idebenone (50 mg/kg), manidipine 2HCl (2 mg/kg) or a combination of idebenone (50 mg/kg) and manidipine 2HCl (2 mg/kg) was administered orally once a day for 3 weeks. In the combination group and manidipine 2HCl-treated group, the neurological deficits after the onset of stroke were ameliorated during the entire experimentalperiod. Especially, the combination significantly decreased the number of days with severe neurological deficits as compared to the control group. The combination and manidipine 2HCl significantly recovered the decrease in body weight and ameliorated the increase of brain weight, which was mainly caused by edema, significantly as compared to the control group. Manidipine 2HCl ameliorated the histological changes in the brain. In the combination group, the histological changes in both the brain and the kidneys were ameliorated. In conclusion, the combination of idebenone and manidipine 2HCl significantly ameliorated the neurological deficits and the histological changes in the brain and the kidney of SHRSP with stroke as compared to each individual treatment. We concluded that manidipine 2HCl enhances the therapeutic effect of idebenone in the treatment of cerebrovascular diseases.
authors.affiliation: Pharmaceutical Research Laboratories I, Takeda Chemical Industries, Ltd. Co., Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nagisa
authors.forename: T
authors.initials: T
authors.lastname: Mihara
authors.forename: K
authors.initials: K
authors.lastname: Hamajo
authors.forename: T
authors.initials: T
authors.lastname: Imamoto
authors.forename: H
authors.initials: H
authors.lastname: Kandori
authors.forename: E
authors.initials: E
authors.lastname: Oda
authors.forename: F
authors.initials: F
authors.lastname: Chatani
authors.forename: A
authors.initials: A
authors.lastname: Nagaoka
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016227:Benzoquinones / Q000008:administration & dosage*; D001921:Brain / Q000473:pathology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000473:pathology; D004095:Dihydropyridines / Q000008:administration & dosage*; D004338:Drug Combinations; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007668:Kidney / Q000473:pathology; D008297:Male; D009578:Nitrobenzenes; D010879:Piperazines; D051381:Rats; D011918:Rats, Inbred SHR; D014451:Ubiquinone / Q000031:analogs & derivatives
chemical_list: D016227:Benzoquinones; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004338:Drug Combinations; D009578:Nitrobenzenes; D010879:Piperazines; D014451:Ubiquinone; C054218:manidipine; C036619:idebenone