PH-DEPENDENT NMDA RECEPTOR ANTAGONISTS

摘要

NMDA receptor blockers, including pH-sensitive NMDA receptor blockers, are provided as neuroprotective drugs that are useful in stroke, traumatic brain injury, epilepsy, and other neurologic events that involve acidification of brain or spinal cord tissue. Compositions and methods of this invention are used for treating neurodegeneration resulting from NMDA receptor activation. The compounds described herein have enhanced activity in brain tissue having lower-than normal pH due to pathological conditions such as hypoxia resulting from stroke, traumatic brain injury, global ischemia tat may occur during cardiac surgery, hypoxia tat may occur following cessation of breathing, pre-eclampsia, spinal cord trauma, epilepsy, chronic pain, vascular dementia and glioma tumors. Compounds described herein are also useful in preventing neurodegeneration in patients with Parkinson's Alzheimer's, Huntington's chorea, ALS, and other neurodegenerative conditions known to the art to be responsive to treatment using NMDA receptor blockers. Preferably the compounds provided herein are allosteric NMDA inhibitors.