INHIBITION OF CONSTITUTIVE AND INDUCIBLE NITRIC-OXIDE SYNTHASE - POTENTIAL SELECTIVE-INHIBITION

Nitric oxide (NO) is a molecule that has been shown to be involved in a diverse array of physiological events. A variety of disease states a nd disorders ale, in fact, due to either an over- or an underproductio n of NO. As a result of the ubiquity and diversity of NO-mediated phen omenon, pharmacological manipulation is difficult. NO biosynthesis is the result of an oxidation of a terminal nitrogen on the amino acid ar ginine by a class of enzymes generally referred to as the nitric oxide synthases (NOSs). Since the various isoforms of NOS are distributed i n cells and tissues according to their function, there is the possibil ity that manipulation of NO levels can be accomplished by designing sp ecific pharmacological agents targeted at a single NOS isoform. Thus, this review discusses general inhibition of the NOSs by a variety of a gents and then focuses on the possibility of developing agents for spe cific isoform inhibition.