H3R antagonist 1

H3R antagonist 1 is a histamine receptor 3 (H3R) inverse agonist. H3R antagonist 1 increases the expression levels of myelin-associated glycoprotein (MAG) and myeline basic protein (MBP) in differentiating oligodendrocytes. H3R antagonist 1 can be used for the study of multiple sclerosis^[1]. IC50 & Target:Histamine receptor 3^[1] In Vitro:H3R antagonist 1 (example 2) promotes oligodendrocyte precursor cell (OPC) differentiation in a dose-dependent manner, at EC₅₀ = 25 nM. Western blot reveals a significant increase in expression levels of two markers of mature oligodendrocytes, myelin-associated glycoprotein (MAG) and myeline basic protein (MBP) in differentiating oligodendrocytes after treatment with H3R antagonist 1, which suggests that treatment with H3R antagonist 1 drives more oligodendrocyte precursor cells to differentiate. H3R antagonist 1 increases the Forskolin (HY-15371)-stimulated cAMP level in the primary oligodendrocyte precursor cells in a dose-dependent manner^[1]. In Vivo:The ability of H3R antagonist 1 (example 2) to enhance in vivo remyelination is determined with the Cuprizone (HY-W115718)/Rapamycin (HY-10219)-induced demyelination model. Mice are treated with Cuprizone diet combined with intraperitoneal injections of Rapamycin for 5 weeks followed by 9 days of compound administration. Cuprizone diet plus intraperitoneal injections of Rapamycin induced severe demyelination in both corpus callosum and cortex and treatment with H3R antagonist 1 (30 mg/kg, 9 days) significantly increases density of myelin specific Black-gold II staining in the lesion of corpus callosum and cortex in forebrain, compared to vehicle control group^[1].