H3R-IN-1 Hydrochloride is an inverse agonist of histamine receptor 3( H3R ) .

Treatment with H3R-IN-1, which is a H3R inverse agonist, promotes oligodendrocyte precursor cell (OPC) differentiation in a dose-dependent manner, at EC 50 =25 nM. Western blot shows 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-IN-1, which reveals that treatment with H3R-IN-1 drives more OPCs to differentiate. H3R-IN-1 increases the Forskolin-stimulated cAMP level in the primary oligodendrocyte precursor cells in a dose-dependent manner [1].

The ability of H3R-IN-1 to enhance remyelination in vivo is determined using the Cuprizone/Rapamycin-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-IN-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].