N,N'-DI-P-BROMOPHENYL GUANIDINE TREATMENT FOR STROKE AT DELAYED TIMEPOINTS

摘要

1,3 di-o-tolylguanidine (DTG) was examined as anti-stroke drug with a broad therapeutic window. DTG activates sigma 1 and 2 receptors. Administration of DTG at 24 hours post-stroke to rats reduces neurodegeneration by 85%; this is the only pharmacological agent that has been used successfully at this delayed timepoint. Treatment with DTG provides protection of neurons exposed to hypoxia and blocks activation of immune cells that are responsible for delayed neurodegeneration associated with stroke. Disclosed is an altered DTG structure, placing a bromide at the para position to increase tissue penetrance and efficacy. Results show that N,N′-di-p-bromophenyl guanidine protects cultured neurons under hypoxic conditions but is more potent than DTG. Moreover, N,N′-di-p-bromophenyl guanidine is as least as efficacious as DTG in treating rats 24 hours after experimental stroke.