Gill R, Lodge D
Royal Veterinary College, Department of Veterinary Basic Sciences, London, U.K.
Neuropharmacology. 1994 Dec;33(12):1529-36. doi: 10.1016/0028-3908(94)90126-0.
LY 215490 (3RS,4aRS,6RS,8aRS)-6-[2-(1(2)H-tetrazole-5- yl)ethyl]decahydroisoquinoline-3-carboxylic acid), a novel, selective, competitive and systemically active AMPA receptor antagonist was tested as a neuroprotective agent against focal ischaemia in a model of permanent MCA occlusion in the rat. LY 215490 was administered at a dose of 10, 30 or 100 mg/kg 30 min prior to and post-MCA occlusion. The animals were allowed to survive for 24 hr, following which time the brains were processed for volumetric analysis of the infarct size. The low dose of LY 215490 was not effective against the infarct volume in the hemisphere, cortex or caudate. The 2 x 30 mg/kg dose of LY 215490 resulted in 25 and 31% protection against the volume of hemispheric and cortical ischaemic damage, respectively. The highest dose of LY 215490 resulted in a reduced neuroprotective effect with 23 and 27% protection against the volume of hemispheric and cortical ischaemic damage, respectively. The slightly reduced neuroprotective effect of the highest dosing regimen may be due to the respiratory problems seen with this dose. Neither of the two neuroprotective doses of LY 215490 produced any reduction in the volume of caudate damage which represents the core of the infarct.
LY 215490（(3RS,4aRS,6RS,8aRS)-6-[2-(1(2)H-四氮唑-5-基)乙基]十氢异喹啉-3-羧酸）是一种新型、选择性、竞争性且具有全身活性的AMPA受体拮抗剂，在大鼠永久性大脑中动脉闭塞模型中作为抗局灶性缺血的神经保护剂进行了测试。LY 215490在大脑中动脉闭塞前后30分钟以10、30或100毫克/千克的剂量给药。让动物存活24小时，之后对大脑进行处理以对梗死灶大小进行体积分析。低剂量的LY 215490对半球、皮质或尾状核的梗死体积无效。2×30毫克/千克剂量的LY 215490分别对半球和皮质缺血性损伤体积产生了25%和31%的保护作用。LY 215490的最高剂量导致神经保护作用降低，分别对半球和皮质缺血性损伤体积产生23%和27%的保护作用。最高给药方案的神经保护作用略有降低可能是由于该剂量出现的呼吸问题。LY 215490的两种神经保护剂量均未使代表梗死核心的尾状核损伤体积有任何减小。
