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 efficacy of H3R-IN-1 in promoting remyelination in vivo is assessed using the Cuprizone/Rapamycin-induced demyelination model. Mice receive a Cuprizone diet and intraperitoneal Rapamycin injections for 5 weeks, followed by 9 days of H3R-IN-1 treatment (30 mg/kg). Cuprizone and Rapamycin induced severe demyelination in the corpus callosum and cortex, and H3R-IN-1 administration significantly increased myelin-specific Black-gold II staining density in the lesions compared to the vehicle control group [1].