Methapyrilene (hydrochloride)

Methapyrilene (Thenylpyramine) hydrochloride is an orally active H1-receptor antihistamine and an anticholinergic agent of the pyridine chemical class. Methapyrilene hydrochloride has hepatotoxicity and can be used as a hepatotoxin that cause periportal hepatic necrosis in vivo^[2] In Vitro: Methapyrilene hydrochloride (650 μM) results in a down-regulation of TF and up-regulation of FTL, while the level of HMOX1 is not changed. Additionally, the levels of CD44 and SOX9 proteins and the expression of PROM1 (CD133), hepatic stem cell-associated markers are increased^[1].
Methapyrilene hydrochloride (650 μM) decreases CYP2E1, CYP3A4, NR1l3, ALB, mRNA expression and increases CD133 expression^[1].
In Vivo: Methapyrilene hydrochloride (oral gavage; 40 or 80 mg/kg; 5 days per week; 6 weeks) results in changes in the expression of classic hepatotoxicity-related marker genes and iron homeostasis-related genes, especially a prominent, dose-dependent down-regulation of the transferrin (Tf) gene and an up-regulation of the ferritin, light chain (FTL) gene in rats^[1].
Methapyrilene hydrochloride (oral gavage; 150 mg/kg; 3 days) causes periportal liver necrosis at high dosage. Methapyrilene is sufficient to induce liver necrosis, or a subtoxic dose of 50 mg/kg/day^[2].