Discovery and development of neuronal nitric oxide synthase inhibitors

The role of neuronally derived nitric oxide (NO) in neurotransmission and n eural injury remains an area of active investigation. NO generation has bee n postulated to be involved in the deleterious events surrounding ischemia/ reperfusion injury either directly or via the production of more reactive oxidants such as peroxynitrite. In our search for novel therapeutics for th e treatment of a variety of neurological diseases including stroke, we have discovered novel, potent, and selective inhibitors of the neuronal nitric oxide synthase (nNOS) isoform. These compounds have proven to be effective in models of ischemia/reperfusion supporting the role of nNOS in these proc esses. The effects of these compounds as well as additional aspects critica l to their development will be presented. (C) 2000 Elsevier Science Inc.