Meclizine 2HCl

Meclizine is a histamine H1 receptor antagonist used to treat nausea and motion sickness, possesses anticholinergic, central nervous system depressant, and local anesthetic effects. ^[1] Meclizine is an agonist ligand for mouse CAR (constitutive androstane receptor), and an inverse agonist for human CAR. Meclizine increases mCAR transactivation in a dose-dependent manner, stimulates binding of steroid receptor coactivator 1 to the murine receptor in vitro. In contrast, meclizine suppresses hCAR transactivation and inhibits the phenobarbital-induced expression of the CAR target genes, cytochrome p450 monooxygenase (CYP)2B10, CYP3A11, and CYP1A2, in primary hepatocytes derived from mice expressing hCAR, but not mCAR. ^[2]

HepG2 cells are cultured in 24-well dishes with DMEM supplemented with 10% charcoal-stripped calf serum. Cells are transfected using calcium phosphate with 100 ng of receptor expression vectors, 300 ng of luciferase reporter plasmids, and 100 ng of pSV2-β-galactosidase as internal control of transfection efficiency. Drugs are added 12 h after transfection, and cells are incubated for an additional 24 h. The cell lysate is assayed for luciferase activity and normalized to β-galactosidase activity.

Meclizine administration to mice increases expression of CAR target genes in a CAR-dependent manner. ^[2] Meclizine silence oxidative metabolism, suppresses apoptotic cell death in a murine cellular model of polyglutamine (polyQ) toxicity. ^[3]