Tsai T H, Beitman R E, Gibson J P, Larson E J
Arzneimittelforschung. 1982;32(8a):962-6.
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.
2-[1-(2,6-二氯苯氧基)-乙基]-2-咪唑啉盐酸盐（洛非西定、Lofetensin和Loxacor）在器官形成期以高达3.0毫克/千克/天的剂量口服给予怀孕大鼠，或以高达15.0毫克/千克/天的剂量口服给予怀孕兔子时，未显示致畸性证据。在生殖研究中，剂量高达1.0毫克/千克/天的雄性或雌性大鼠，以及剂量高达1.5毫克/千克/天的雄性或雌性兔子，其受孕或妊娠均未受影响。大鼠剂量为1.0毫克/千克/天和兔子剂量为6.4毫克/千克/天会降低新生仔鼠的存活率和生长率，大鼠剂量为3.0毫克/千克/天以及兔子剂量为5.0毫克/千克/天或更高会导致胎儿体重减轻和着床后损失增加。由于新生仔鼠的影响仅在母鼠出现临床体征的剂量下发生（大鼠为1.0毫克/千克/天，兔子为1.5毫克/千克/天，分别相当于人类治疗剂量的100倍或150倍），且胎儿的影响仅在导致一些母鼠死亡的剂量下出现，因此洛非西定产生的不良胎儿和新生仔鼠影响归因于母体毒性，而非对胎儿或新生儿的直接影响。
