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Methylation and Catecholamine Clearance Severe undermethylation with low SAM or elevated SAH may reduce SAM-dependent methyltransferase activity involved in catecholamine metabolism, potentially prolonging nighttime arousal

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In further embodiments, the invention encompasses a method of providing muscular therapy by contacting a cell expressing NNMT with a NNMT inhibitor (such as a cation of Formula I or IA, or otherwise disclosed herein) and one or more chemical entities (e.g., nicotinamide riboside, nicotinamide mononucleotide) that modulates intracellular NAD+ levels to provide muscular therapy