Methapyrilene (hydrochloride)

Methapyrilene is a histamine H₁ receptor antagonist (K_i = 4.5 nM) and non-genotoxic carcinogen.^1,2 Dietary administration of methapyrilene (0.1%) induces liver tumors in rats, with greater than 50% of rats incurring distant metastases.³ It decreases the acetylation of histone 3 lysine 9 (H3K9) and H3K56, as well as the di- and trimethylation of H3K4 and H4K20, respectively, in rat liver when administered at 40 mg/kg per day for six weeks.² Methapyrilene also increases 4-hydroxy nonenal (4-NHE) protein adducts in rat liver. Formulations containing methapyrilene were previously used as sleep aids.

1.Tran, V.T., Chang, R.S.L., and Snyder, S.H.Histamine H1 receptors identified in mammalian brain membranes with [3H]mepyramineProc. Natl. Acad. Sci. U.S.A.75(12)6290-6294(1978) 2.Shpyleva, S., Dreval, K., de Conti, A., et al.Editor's highlight: Organ-specific epigenetic changes induced by the nongenotoxic liver carcinogen methapyrilene in fischer 344 ratsToxicol. Sci.156(1)190-198(2017) 3.Lijinsky, W., Reuber, M.D., and Blackwell, B.N.Liver tumors induced in rats by oral administration of the antihistaminic methapyrilene hydrochlorideScience209(4458)817-819(1980)