Selective Neuronal Nitric Oxide Synthase Inhibitors

Erik   P.   Erdal; Elizabeth   A.   Litzinger; Jiwon      Seo; Yaoqiu      Zhu; Haitao      Ji; Richard   B.   Silverman

Abstract

This review includes the non-patent literature up to October 2004 that deals with selective neuronal nitric oxide synthase inhibitors (highest potency is for the neuronal isozyme). Some non-selective inhibitors or selective inducible nitric oxide synthase inhibitors are mentioned if they are related to compounds that are discussed; structures of these compounds generally are not given. In vitro inhibition constants are given either as IC50 values or as Ki values. An IC50 value, the inhibitor concentration that produces 50% inhibition in the presence of a constant concentration of substrate, is obtained by extrapolation of several rate data points to 50% inhibition. Ki values are derived from several types of plots that relate the concentration of inhibitor with enzyme velocity in the presence of a variety of substrate concentrations [1]. The Ki value can be estimated from the IC50 value [2]. Although the two inhibition constants are related, they are not the same; generally, the reported Ki values tend to be lower than the IC50 values. If specifics are desired about how the data were collected, then the reader will have to look in the literature cited. No attempt was made to be exhaustive in citing all references related to specific inhibitors; rather, examples of literature references are given for each inhibitor described.

Keywords: cell-signaling agent, l-arginine, endothelial cells, macrophage, nos isoforms, protein-protein interactions, guanidine, isothioureidos, tetrahydrobiopterin, calmodulin