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Nitric Oxide (NO)
During the 1980s, NO was identified as a critical regulatory molecule in the human body, in 1992 was named the "Molecule of the Year" by Science, and in 1998 the Nobel Prize in Physiology and Medicine was awarded for this discovery.  NO has diverse roles both in normal and pathological processes including the regulation of blood pressure, neurotransmission, and macrophage defense systems.

Nitric Oxide Synthase (NOS)
NO is synthesized by three isoforms of nitric oxide synthases (NOS) found in endothelial cells (eNOS), neuronal cells (nNOS) and macrophages (iNOS), and this family of enzymes serves different functions.

NOS Enzymes

NOS image

Excess NO in the central nervous system has been implicated in pain sensations caused by migraine, nerve injury and neuropathic pain. Therefore, inhibition of nNOS has the potential to be beneficial in controlling these pain states, and NeurAxon is the first company to have developed and tested in human clinical trials a product candidate possessing selective nNOS inhibition.

Scientific Articles About NOS

2007

Jain K, “Nitric Oxide Therapeutics, Markets and Companies” Jain PharmaBiotech July 2007

Maddaford, S. et al, “Emerging Frontiers of Designed Multiple Ligands.  Rationale Design of Dual Action Nitric Oxide Synthase Inhibitors with 5HT Agonism for the Treatment of MigraineCSC2007 Abstract, Winnipeg

Patman, J. et al, “Novel 2-aminobenzothiazoles as selective neuronal nitric oxide synthase inhibitorsBiorganic Medicinal Chemistry Letters 2007 May 1;17(9):2540-4. Epub 2007 Feb 8

2006

Patman, J. et al, “Novel Aminobenzothiazole Nitric Oxide Synthase Inhibitors.  Applications in the Treatment of Central Nervous System DisordersCSC2006 Abstract, Halifax

Patman J. et al, “Novel neuronal Nitric Oxide Synthase (nNOS) Inhibitors in Models of Chronic PainCSC2006 Abstract, Halifax

2005 and earlier

Afridi S, Kaube H and Goadsby PJ, “Occipital activation in glyceryl trinitrate induced migraine with visual auraJ. Neurol. Neurosurg. Psychiatry 2005;76;1158-1160 doi:10.1136/jnnp.2004.050633

van der Kuy P, Lohman J, “The role of nitric oxide in vascular headachePharm World Sci 2003; 25(4): 146-151

Thomsen L, Olesen J, “Nitric Oxide Theory of Migraine” Clinical Neuroscience 1998

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