Nitric oxide donors - current trends in therapeutic applications

Abstract

The nitric oxide (NO) radical, endogenously produced from L-arginine, is a natural vasodilator also involved in many other physiological and pathological processes. The increasing knowledge of the multiple roles of NO keeps extending its range of potential therapeutic applications. However, these many applications require individually designed exogenous molecular sources of NO. To date, NO donors such as diazeniumdiolates, S-nitrosothiols, sydnonimines, nitroso complexes, organic nitrates and nitrites are claimed to be useful for the treatment of cardiovascular, renal, respiratory, gastrointestinal, neurodegenerative, inflammatory and infectious diseases. Development of new NO donors differs from common drug development because the active drug (NO) has already been determined, therefore research involves the development of devices to deliver NO. An alternative strategy is to link an NO releasing moiety to other well-established bioactive molecules creating NO donor hybrids. Different hybrid compounds can offer various drug actions with synergistic effects, reduced toxicity and no detrimental side effects. Among others, Hou, Janczuk and Wang [1], and a few years previously Stamler and Feelisch [2], have issued systematic and comprehensive reviews on NO donors. In view of the huge number of publications on this topic, this article will restrictively focus on NO donors and pathological situations and diseases which are claimed in the important therapeutic patents issued between 1997 and 2000. Table 1 gives the relevant diseases and classes of NO donors, gathered from these patents.

• L-arginine
• diazeniumdiolates
• erectile dysfunction
• hybrid compounds
• infertility
• molsidomine
• nitric oxide donors
• nitric oxide
• organic nitrates
• organic nitrites
• SIN-1
• S-nitrosothiols
• vasodilatation
• vasospasm