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Methods for treating central or peripheral nervous system damage

机译:治疗中枢或周围神经系统损害的方法

摘要

A composition comprising a novel Ca2+-activated, [ATP]i-sensitive nonspecific cation (NCCa-ATP) channel is described. The channel is found in mammalian neural cells and exhibits a different sensitivity to block by various adenine nucleotides, and is activated by submicromolar [Ca]i. The NCCa-ATP channel is activated under conditions of ATP depletion, which causes severe cell depolarization, followed by cell swelling. The NCCa-ATP channel is regulated by a sulfonylurea receptor and is inhibited by sulfonylurea compounds glibenclamide and tolbutamide. Methods employing compositions comprising the NCCa-ATP channel to screen for compounds that block the channel and the use of such antagonists as therapeutics in preventing brain swelling and damage are described. In addition, methods employing compositions comprising the Kir2.3 channel to screen for compounds that open the channel and the use of such antagonists as therapeutics in preventing brain swelling and damage are described.
机译:描述了一种包含新颖的Ca 2 + 活化的[ATP] i 敏感非特异性阳离子(NC Ca-ATP )通道的组合物。该通道在哺乳动物神经细胞中发现,对各种腺嘌呤核苷酸的阻断具有不同的敏感性,并被亚微摩尔[Ca] i 激活。 NC Ca-ATP 通道在ATP耗尽的条件下被激活,这会导致严重的细胞去极化,进而引起细胞肿胀。 NC Ca-ATP 通道受磺酰脲受体调节,并受到磺酰脲类化合物格列本脲和甲苯磺丁酰胺的抑制。描述了采用包含NC Ca-ATP 通道的组合物筛选阻断该通道的化合物的方法,以及使用此类拮抗剂作为预防脑肿胀和损伤的治疗剂的方法。另外,描述了使用包含Kir2.3通道的组合物筛选打开该通道的化合物的方法,以及使用此类拮抗剂作为预防脑肿胀和损伤的治疗剂的方法。

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