Meclizine dihydrochloride (NSC28728) is a histamine H1 antagonist used in the treatment of motion sickness, vertigo, and nausea during pregnancy and radiation sickness.

Meclizine increases the expression of mouse CAR target genes in a CAR-dependent manner.

In vitro, Meclizine exhibits dose-dependent augmentation of mCAR transactivation and enhances the recruitment of the coactivator SRC-1 (steroid receptor coactivator-1) to the receptor. Conversely, in mouse hepatocytes expressing only hCAR and not mCAR, Meclizine inhibits hCAR transcriptional activation and suppresses the expression of luminal-induced CAR downstream genes, which include CYP2B10, CYP3A11, and CYP1A2 (cytochrome P450 monooxygenases). Therefore, Meclizine acts as an agonist ligand for mouse CAR (constitutive androstane receptor) but as a reverse agonist for human CAR.

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.(Only for Reference)