SELECTIVE INHIBITORS OF NEURONAL NITRIC-OXIDE SYNTHASE - IS NO NOS REALLY GOOD NOS FOR THE NERVOUS-SYSTEM

It is now ten years since NO was shown to account for the biological a ctivity of endothelium-derived relaxing factor (EDRF). It is also the tenth anniversary of the identification of L-N-G monomethyl arginine ( L-NMMA) as the very first inhibitor of NO biosynthesis. That EDRF and NO were one and the same sparked an explosion of interest in the bioch emistry and pharmacology of NO which has yet to subside. In contrast, the first ever nitric oxide synthase (NOS) inhibitor slipped seamlessl y into the literature virtually without comment at the time. Over the following decade, L-NMMA (and like NOS inhibitors) have proved invalua ble as tools for probing the biological roles of NO in health and dise ase and, in particular, have increased our understanding of the functi on of NO in the nervous system. Further advances in this important are a now require the development of inhibitors selective for the neuronal isoform of NOS (nNOS). Here, Philip Moore and Rachel Handy provide an up-to-date account of the literature regarding the biochemical and ph armacological characterization of NOS inhibitors with particular refer ence to compounds with greater selectivity for the nNOS isoform.