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US 2014/0235564 A1Published application
Methods for treating neural cell swelling
AssigneeUniversity of Maryland, Baltimore
InventorsJ. Marc Simard, Mingkui Chen
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AssigneeUniversity of Maryland, Baltimore
InventorsJ. Marc Simard, Mingkui Chen
Estimating the term…
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.
1-43. (canceled)
A method of treating a subject having brain injury or cerebral ischemia, comprising the step of administering an antagonist of a NCCa-ATP channel that blocks the channel, prevents the channel opening, and/or (3) reduces the magnitude of membrane current through the channel.
A method of treating a subject having brain injury or cerebral ischemia by administering to the subject an antagonist of a NCCa-ATP channel in a dose at a substantially constant level for a given period of time.
A method of treating brain swelling in an individual, comprising the step of administering to the individual a compound that modulates NCCa-ATP channel activity.
A method of treating a subject for central or peripheral nervous system damage, said damage comprising depolarization due to expression of a NCCa-ATP channel in neural cells, said method comprising administering to the subject a formulation comprising an effective amount of a compound effective to inhibit a NCCa-ATP channel in the neural cells and a pharmaceutically acceptable carrier, wherein the compound is a sulfonylurea receptor 1 (SUR1) antagonist selected from a sulfonylurea compound, a benzamido derivative, an imidazoline derivative, and a combination thereof, wherein said administration of the SUR1 antagonist inhibits the activity of said NCCa-ATP channel in neural cells expressing the channel.
Dependencies are inferred from the claim text.