CHLORCYCLIZINE is a histamine H1 antagonist and a potent hepatitis C virus (HCV) entry inhibitor.

Pregnant rats were administered 30, 60, or 90 mg/kg CHLORCYCLIZINE on Gestation Days 11 to 14. Fetal palate gene expression was also assessed after 90 mg/kg CHLORCYCLIZINE at 8, 15 and 30 hours post-dose on Gestation Day 14 using microarray and qRT-PCR. Rats in the 60- and 90-mg/kg groups exhibited adverse clinical signs and body weight loss. Rats in the 90-mg/kg group also demonstrated increases in late resorptions and decreases in fetal weight. Effects in the low-dose group were limited to decreases in body weight gain. Fetal assessment on Gestation Day 21 revealed that findings were limited to the 60- and 90-mg/kg groups, and included cleft palate (80% of litters for both groups), high arched palate, small nose, micrognathia, high domed head, digits shortened/absent and small limb. The fetal incidence of cleft palate was higher at 90 mg/kg, thus this dose was selected to assess palate gene expression. The altered genes associated with CHLORCYCLIZINE-induced cleft palate included Wnt5a, Bmp2, Bmp4, Fgf10, Fgfr2, Msx1, and Insig1 but the magnitude of the change was relatively small (1.5- to 2-fold)[1].