Radical releasing properties of nitric oxide donors GEA 3162, SIN-1 and S-nitroso-N-acetylpenicillamine

Eur J Pharmacol. 1998 Apr 3;346(1):97-102. doi: 10.1016/s0014-2999(98)00009-0.

Abstract

The nitric oxide (NO)-, superoxide anion (O2.-)- and peroxynitrite (ONOO-)-releasing properties of 1,2,3,4-oxatriazolium,5-amino-3-(3,4-dichlorophenyl)-chloride (GEA 3162) were characterized and compared with the known NO-donors 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine. All the three compounds released NO in aqueous solutions in a dose-dependent manner as measured by ozone-chemiluminescence. GEA 3162 produced more NO than SIN-1, but less than S-nitroso-N-acetylpenicillamine during a 45 min incubation time. SIN-1 reduced nitro blue tetrazolium and the effect was inhibitable by superoxide dismutase. Reduction of nitro blue tetrazolium was not detected in the solutions of GEA 3162 and S-nitroso-N-acetylpenicillamine suggesting that SIN-1 but not GEA 3162 and S-nitroso-N-acetylpenicillamine release O2.- in their decomposition process. Formation of ONOO- in solutions of GEA 3162, SIN-1 and S-nitroso-N-acetylpenicillamine was estimated indirectly by measuring 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 3162 produces negligible amounts of O2.- 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 biological activity of oxatriazole derivatives as compared to SIN-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Molsidomine / analogs & derivatives*
  • Molsidomine / chemistry
  • Nitric Oxide / chemical synthesis*
  • Oxygen / chemistry
  • Penicillamine / analogs & derivatives*
  • Penicillamine / chemistry
  • Superoxides / chemical synthesis
  • Triazoles / chemistry*
  • Tyrosine / analogs & derivatives
  • Tyrosine / chemical synthesis

Substances

  • S-nitro-N-acetylpenicillamine
  • Triazoles
  • Superoxides
  • Nitric Oxide
  • Tyrosine
  • linsidomine
  • GEA 3162
  • Molsidomine
  • Penicillamine
  • Oxygen