A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 35/30 (2006.01) A61K 31/00 (2006.01) A61K 31/426 (2006.01) A61K 31/4439 (2006.01) A61K 31/64 (2006.01) A61K 45/00 (2006.01) A61P 29/00 (2006.01) C07K 14/705 (2006.01) G01N 33/567 (2006.01) G01N 33/68 (2006.01)
Patent
CA 2477812
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.
L'invention concerne une composition comprenant un nouveau canal (NC¿Ca-ATP?) cationique non spécifique sensible à la [ATP]¿i?, activé par du Ca?2+¿. Ce canal se situe dans des cellules neuronales mammifères et présente une sensibilité différente au blocage par des nucléotides à adénine diverses, et est activé par du [Ca]¿i? submicromolaire. Le canal NC¿Ca-ATP? est activé dans des conditions de déplétion en ATP, provoquant une dépolarisation cellulaire sévère, suivie d'un oedème cérébral. Ledit canal NC¿Ca-ATP? est régulé par un récepteur aux sulfonylurées et est inhibé par des composés sulfonylurés glibenclamide et tolbutamide. L'invention concerne également des procédés faisant intervenir des compositions comprenant le canal NC¿Ca-ATP? destinés au criblage de composés qui bloquent le canal, ainsi que des procédés mettant en oeuvre de tels antagonistes en tant que médicaments dans la prévention d'oedèmes cérébraux et de lésions cérébrales. L'invention concerne en outre des procédés faisant intervenir des compositions comprenant le canal Kir2.3 destinés à cribler des composés qui ouvrent le canal, ainsi que des procédés mettant en oeuvre de tels antagonistes en tant que médicaments dans la prévention d'oedèmes cérébraux et de lésions cérébrales.
Chen Mingkui
Simard J. Marc
Borden Ladner Gervais Llp
University Of Maryland Baltimore
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