Blocking NO synthesis: how, where and why?
Nitric oxide (NO) is a key physiological mediator, and the association of disordered NO generation with many pathological conditions has led to much interest in pharmacologically modulating NO levels. However, the wide range of processes in which NO has been implicated, and the fact that increases or decreases in NO levels might be therapeutically desirable depending on the condition or even at different stages of the same condition, pose considerable challenges for drug development. Here, we focus on the rationale and potential for approaches that reduce NO synthesis, which have led to the development of several compounds that will shortly be entering clinical trials.
Vallance
Patrick
P
Centre for Clinical Pharmacology, British Heart Foundation Laboratories, Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK. patrick.wallance@ucl.ac.uk
Leiper
James
J
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; C496320:NOS1 protein, human; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III