AM-36, a novel neuroprotective agent, profoundly reduces reactive oxygen species formation and dopamine release in the striatum of conscious rats after endothelin-1-induced middle cerebral artery occlusion

Abstract

Elevated generation of reactive oxygen species (ROS) has been demonstrated during ischemia and reperfusion. Dopamine (DA) autooxidation may contribute to increased ROS generation. The novel neuroprotective agent AM-36 has antioxidant and Na+ channel blocking activity and reduces neuronal damage in both cortex and striatum after middle cerebral artery (MCA) occlusion. Here we sought in vivo evidence of the ability of AM-36 to inhibit intrastriatal ROS generation and DA release after ischemia. Salicylate hydroxylation coupled with in vivo microdialysis in the striatum of conscious Long Evans rats was performed during MCA occlusion by perivascular microinjection of endothelin-1 (ET-1). AM-36 (6..