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Methapyrilene is a histamine H1 receptor antagonist (Ki = 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.

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