Pk. Moore et Rlc. Handy, SELECTIVE INHIBITORS OF NEURONAL NITRIC-OXIDE SYNTHASE - IS NO NOS REALLY GOOD NOS FOR THE NERVOUS-SYSTEM, Trends in pharmacological sciences, 18(6), 1997, pp. 204-211
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.