Pharmacological Screen to Identify Compounds That Facilitate NO signaling in Muscle With Deficient nNOS Localization and/or Activity

Technology DescriptionResearchers have discovered a newoption for treating muscular dystrophy and other diseases associated withmuscle wasting symptoms. This option consists of the administration ofsildenafil (or another inhibitor of phosphodiesterase 5A) in affected patients priorto exercise or similar activity. The effects of this treatment areattributed to the known mechanism of action for these agents, which is theprevention of cGMP degradation. cGMP is a key messenger for initiatingvasodilation and thus increasing blood flow. When this treatment is instituted,the cGMP persists longer in smooth muscle cells and the resulting vasodilationalso persists for a greater period of time. This increase in blood flow toactive muscles slows their rate of fatigue and limits the activity-inducedmuscle tissue damage associated with myopathic conditions.Advantages Novel mechanism of action. Phosphodiesterase inhibitors work via the preservation of cGMP in blood vessels, which initiates vasodilation. It is believed that the absence of vasodilation and the resulting lack of increased blood flow play a key role in rapid muscle fatigue and muscle cell breakdown.Well-established safety profile. Sildenafil and other phosphodiesterase inhibitors have been used clinically for many years and have shown themselves to be safe for long-term use.

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