Finnell R H, Shields H E, Taylor S M, Chernoff G F
Teratology. 1987 Apr;35(2):177-85. doi: 10.1002/tera.1420350203.
Anticonvulsant drugs are widely prescribed medications known to complicate more than 11,500 pregnancies each year in the United States. Although there is no clear consensus as to the teratogenicity of all of the clinically available compounds, it appears that most anticonvulsant drugs can induce congenital abnormalities in susceptible individuals. In a study designed to examine the role of the genotype on sensitivity to phenobarbital-induced malformations, three highly inbred mouse strains (SWV, C57BL/6J, and LM/Bc) received the drug via chronic oral administration. Phenobarbital was found to have a significant teratogenic potential in mice, resulting in skeletal, cardiac, renal, neural, and urogenital defects in a dose-related fashion. The LM/Bc strain was most sensitive to phenobarbital, with 46.7% of the fetuses exposed to the highest maternal plasma concentrations having malformations. C57BL/6J fetuses were the most resistant strain, with only 28.6% abnormalities.
抗惊厥药物是广泛使用的处方药,在美国每年有超过11500例妊娠因这些药物而变得复杂。尽管对于所有临床可用化合物的致畸性尚无明确共识,但似乎大多数抗惊厥药物都能在易感个体中诱发先天性异常。在一项旨在研究基因型对苯巴比妥诱导畸形敏感性作用的研究中,三种高度近交的小鼠品系(SWV、C57BL/6J和LM/Bc)通过长期口服给予该药物。发现苯巴比妥在小鼠中具有显著的致畸潜力,以剂量相关的方式导致骨骼、心脏、肾脏、神经和泌尿生殖系统缺陷。LM/Bc品系对苯巴比妥最敏感,暴露于最高母体血浆浓度的胎儿中有46.7%出现畸形。C57BL/6J胎儿是最具抗性的品系,只有28.6%出现异常。