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 that may occur during cardiac surgery, hypoxia that 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.