Authors: Burgaud, J.L.; Riffaud, J.P.; Soldato, P.

Source: Current Pharmaceutical Design, Volume 8, Number 3, 1 February 2002 , pp. 201-213(13)

Publisher: Bentham Science Publishers

Abstract:

Nitric oxide (NO) deficiency has been implicated in many pathological and physiological processes within the mammalian body providing a plausible biologic basis for the use of NO replacement therapy in these conditions. Exogenous NO sources may hopefully constitute a powerful way to supplement NO when the body cannot generate enough for normal biological functions.

This theory has opened up the possibility of designing new drugs that are capable of delivering NO into tissues and the bloodstream in a sustained and controlled manner. This objective has been reached by grafting an organic nitrate structure onto existing molecules with various spacers such as aliphatic or aromatic chain, with different degree of complexity.

This approach has led to the synthesis of several new chemical entities in various pharmacological classes, whose profile seems to challenge the parent drug not only on the basis of new pharmacological properties but also on a better toxicological and safety profile.

In this article, general aspects on NO and NO donors are reviewed. Major focus is placed upon recent developments of novel NO donors, NO releasing device(s) as well as innovative improvements to conventional NO donors. Several examples are given in some important therapeutic indications such as cardiovascular diseases (NO-aspirin), pain and inflammation (NO-paracetamol), osteoporosis and urinary incontinence (NO flurbiprofen with aliphatic spacer), Alzheimer's disease (NO-flurbiprofen with anti-oxidant spacer), respiratory disorders (NO-steroids).

Keywords: Nitric-Oxide Releasing Molecules; iNOs (inducible NO synthase); Rationale; Bronchodilation; NO-flurbiprofen

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612023396357

Publication date: 2002-02-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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