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" Chapter 2 Advancements in the Development of Nitric Oxide Synthase Inhibitors "
Shawn Maddaford
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BL
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786430
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b606445
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Shawn Maddaford
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Chapter 2 Advancements in the Development of Nitric Oxide Synthase Inhibitors\ Shawn Maddaford
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9780123747662
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| Abstract
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This chapter focuses on recent advances in the design of the selective inhibitors of nitric oxide synthase (NOS) and some of the emerging preclinical and clinical developments of these newer inhibitors. In addition to its role in regulating blood pressure, NO is important in platelet aggregation, bone remodeling, inflammation, and neurotransmission, wherein NO initiates changes in neuronal excitability and synaptic strength by acting at pre- and/or post-synaptic locations. The reduction in pathophysiological levels of NO through the inhibition of NOS has the potential to be therapeutic in a multitude of indications including the treatment of septic shock, stroke, neurodegenerative disorders, and in the treatment of pain. However, the therapeutic control of NO synthesis has, until recently, been unattainable due to the difficulties in achieving isoform-selective inhibition. The selective inhibition of the neuronal NOS (nNOS) enzyme and/or the inducible NOS (iNOS) enzyme over the endothelial NOS (eNOS) enzymes for the treatment of pain or migraine is required to avoid the cardiovascular liabilities associated with eNOS inhibition. Therefore, targeting isoforms of NOS may be a valid strategy to produce novel mechanism-based therapeutics.
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Jailall Ramnauth
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Shawn Maddaford
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Subhash C Annedi
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Suman Rakhit Affiliation: NeurAxon Inc, 480 University Ave, Suite 900, Toronto, ON M5G 1V2, Canada
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