Teratologic and reproductive studies of lofexidine

2-[1-(2,6-Dichlorphenoxy)-ethyl]-2-imidazoline hydrochloride (lofexidine, Lofetensin and Loxacor) elicited no evidence of teratogenicity when administered orally during the period of organogenesis to pregnant rats at doses up to 3.0 mg/kg/day or to pregnant rabbits at doses up to 15.0 mg/kg/day. In reproductive studies there were no effects on conception or pregnancy in male or female rats at dosages up to 1.0 mg/kg/day or male or female rabbits at dosages up to 1.5 mg/kg/day. Dosages of 1.0 mg/kg/day in rats and 6.4 mg/kg/day in rabbits reduced survival and growth rates of neonates and dosages of 3.0 mg/kg/day in rats and 5.0 mg/kg/day or more in rabbits caused reduced fetal weights and increased postimplantation losses. Since neonatal effects occurred only at dosages which produced clinical signs in the dams (1.0 mg/kg/day in rats and 1.5 mg/kg/day in rabbits which correspond to 100 or 150 times, respectively, the therapeutic dose in man) and since fetal effects occurred only at those dosages which caused some maternal deaths, the adverse fetal and neonatal effects produced by lofexidine were attributed to maternal toxicity rather than a direct effect on the fetus or newborn.