Nitric oxide (NO)-related pharmaceuticals: Contemporary approaches to therapeutic NO modulation

The biologically important gaseous radical, nitric oxide (NO), is a versatile chemical entity that enters into regulatory, protective, and adverse interactions with biomolecules and cells, in some cases through NO-derived nitrogen oxide species. Both excess tissue NO and its insufficiency have been implicated in the genesis or evolution of several important disease states. The associated medical needs and commercial opportunities have fostered attempts to modulate tissue NO tone for symptomatic benefit or therapeutic gain. State-of-the-art strategies for NO modulation in contemporary drug discovery and development encompass sexual dysfunction, cardiovascular, and antiinflammatory indications. Increased understanding of NO's physiological chemistry and ways to target its pharmacology appear critical to the successful clinical exploitation of NO's diverse properties. Integration of research on both the basic science of NO's mechanistic biology and the applied science of drug discovery and development represents a millennium mandate to the pharmaceutical industry in the area of NO-related therapeutics. (C) 2000 Elsevier Science Inc.