Methods for treating brain swelling with a compound that blocks a non-selective cation channel

摘要

The present invention is directed to therapeutic compounds, treatment methods, and kits affecting the NCCa-ATP channel of neural tissue, including neurons, glia and blood vessels within the nervous system, and methods of using same. The NCCa-ATP channel is newly expressed in neural tissue following injury such as ischemia, and is regulated by the sulfonylurea receptor SUR1, being inhibited by sulfonylurea compounds, e.g., glibenclamide and tolbutamide, and opened by diazoxide. Antagonists of the NCCa-ATP channel, including SUR1 antagonists, are useful in the prevention, diminution, and treatment of injured or diseased neural tissue, including astrocytes, neurons and capillary endothelial cells, that is due to ischemia, tissue trauma, brain swelling and increased tissue pressure, or other forms of brain or spinal cord disease or injury. Agonists of the NCCa-ATP channel may be are useful in the treatment neural tissue where damage or destruction of the tissue, such as a gliotic capsule, is desired.

主权项

1. A method of ameliorating the effect of a reduction in blood flow in peri-infarct brain tissue in ischemic disease or injury in a subject comprising administering to a subject having a reduction in blood flow in peri-infarct brain tissue in ischemic disease or injury an amount of a compound that is effective to inhibit the activity of a NCCa-ATP channel in a neuronal cell, a neuroglia cell, or a neural endothelial cell and that is effective to ameliorate the effect of a reduction in blood flow in peri-infarct brain tissue in ischemic disease or injury, wherein the compound is a sulfonylurea compound, a benzamido derivative, an imidazoline derivative, or a combination thereof, and wherein the effect of said reduction in said blood flow in peri-infarct brain tissue in said ischemic disease or said injury in the subject is ameliorated.