RADICAL RELEASING PROPERTIES OF NITRIC-OXIDE DONORS GEA 3162, SIN-1 AND S-NITROSO-N-ACETYLPENICILLAMINE

The nitric oxide (NO)-, superoxide anion (O-2(-))- and peroxynitrite ( ONOO-)-releasing properties of triazolium,5-amino-3-(3,4-dichloropheny l)-chloride (GEA 3162) were characterized and compared with the known NO-donors 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenic illamine. All the three compounds released NO in aqueous solutions in a dose-dependent manner as measured by ozone-chemiluminescence. GEA 31 62 produced more NO than SIN-1, but less than S-nitroso-N-acetylpenici llamine during a 45 min incubation time. SIN-1 reduced nitro blue tetr azolium and the effect was inhibitable by superoxide dismutase. Reduct ion of nitro blue tetrazolium was not detected in the solutions of GEA 3162 and S-nitroso-N-acetylpenicillamine suggesting that SIN-1 but no t GEA 3162 and S-nitroso-N-acetylpenicillamine release O-2(-) in their decomposition process. Formation of ONOO- in solutions of GEA 3162, S IN-1 and S-nitroso-N-acetylpenicillamine was estimated indirectly by m easuring the formation of nitrotyrosine. The data indicate that ONOO- was produced in the presence of SIN-1 but not in solutions of GEA 3162 and S-nitroso-N-acetylpenicillamine. The results suggest that GEA 316 2 produces negligible amounts of O-2(-) and ONOO- as compared to SIN-1 . This adds the value of GEA 3162 as an useful tool in NO research and could well explain the earlier findings on the superior NO-like biolo gical activity of oxatriazole derivatives as compared to SIN-1. (C) 19 98 Elsevier Science B.V.