Development of 3-nitratomethyl-PROXYL (NMP): A novel, bifunctional superoxide dismutase-mimic-nitric oxide-donor

Abdullah Haj-Yehia*, Taher Nassar, Chaim Lotan, Thomas Münzel, Leslie Benet, Erik E. Änggard

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations


The vascular endothelium plays a central role in the regulation of physiological functions through the formation, release, and action of various vasoactive factors. Of these, in particular, impairment of activity of locally released nitric oxide (NO) plays a major role in endothelial dysfunction. This dysfunction contributes largely to changes in vascular structure and growth and adhesivity to platelets and leukocytes, resulting in atherosclerosis and thrombosis which ultimately lead to coronary artery disease (CAD). Nitrovasodilators constitute a group of compounds referred to collectively as 'NO-donors.' Of these NO-donors, the organic nitrate glyceryl trinitrate (GTN) has been the mainstay in treatment of angina pectoris accompanying CAD. Unfortunately, however, early development of tolerance to the vasodilatory effect of the drug, usually accompanied by increased response of blood vessels to endogenous vasoconstrictors (rebound phenomenon), constitutes a major drawback of nitrate therapy. Several mechanisms have been proposed to underlie development of tolerance to organic nitrates and cross-tolerance to other NO-donors. Of these, recent reports indicate the primary involvement of superoxide (SO) in mediation of tolerance. Based on these reports and on growing evidence from our laboratories, we herein report the development of a novel organic nitrate; 3-nitratomethyl-PROXYL (NMP) that, in addition to being a classical NO-donor, also possesses a potent antisuperoxide (SOD-mimic) action. As such, NMP is probably the first compound that can simultaneously and favorably affect both NO and SO. This simultaneous bifunctionality may underlie the potent vasodilatory action of NMP without induction of tolerance. Since the ratio between NO and SO constitutes a major determinant of cellular function, bifunctional agents like NMP may prove useful in the pharmacotherapeutic management of a long series of oxidative stress-mediated pathologies in which an imbalance between NO and SO exists. (C) 2000 Wiley-Liss, Inc.

Original languageAmerican English
Pages (from-to)528-536
Number of pages9
JournalDrug Development Research
Issue number3-4
StatePublished - 2000


  • NO
  • Nitrates
  • Nitroxides
  • SOD
  • Superoxide
  • Tolerance


Dive into the research topics of 'Development of 3-nitratomethyl-PROXYL (NMP): A novel, bifunctional superoxide dismutase-mimic-nitric oxide-donor'. Together they form a unique fingerprint.

Cite this