Nitrates and no release: Contemporary aspects in biological and medicinal chemistry

Gregory R.J. Thatcher, Adrian C. Nicolescu, Brian M. Bennett, Violeta Toader

Research output: Contribution to journalReview articlepeer-review

131 Scopus citations

Abstract

Nitroglycerine has been used clinically in the treatment of angina for 130 years, yet important details on the mechanism of action, biotransformation, and the associated phenomenon of nitrate tolerance remain unanswered. The biological activity of organic nitrates can be said to be nitric oxide mimetic, leading to recent, exciting progress in realizing the therapeutic potential of nitrates. Unequivocally, nitroglycerine and most other organic nitrates, including NO-NSAIDs, do not behave as NO donors in the most fundamental action: in vitro activation of sGC to produce cGMP. The question as to whether the biological activity of nitrates results primarily or exclusively from NO donation will not be satisfactorily answered until the location, the apparatus, and the mechanism of reduction of nitrates to NO are defined. Similarly, the therapeutic potential of nitrates will not be unlocked until this knowledge is attained. Aspects of the therapeutic and biological activity of nitrates are reviewed in the context of the chemistry of nitrates and the elusive efficient 3e - reduction required to generate NO.

Original languageEnglish (US)
Pages (from-to)1122-1143
Number of pages22
JournalFree Radical Biology and Medicine
Volume37
Issue number8
DOIs
StatePublished - Oct 15 2004
Externally publishedYes

Keywords

  • Biotransformation
  • cGMP
  • Free radicals
  • Nitrate
  • Nitration
  • Nitric oxide
  • Nitrosation
  • Signaling

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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