Nomura T, Isa Y, Kurokawa N, Kanzaki T, Tanaka H, Tada E, Sakamoto Y
Toxicology. 1984 Feb;29(4):281-91. doi: 10.1016/0300-483x(84)90160-4.
Aminopyrine and its compound with barbital have been used in humans as analgesics and antipyretics. A compound, pyrabital (2 molecules of aminopyrine and 1 molecule of barbital) given daily on Days 9, 10 and 11 of gestation produced significant yields of fetal deaths and malformations in ICR/Jcl mice. Most malformations induced were ruptured omphaloceles (eventration of the abdominal viscera), which were associated with malrotation of the intestine, cleft palates, and tail anomalies, finger and toe anomalies. Aminopyrine also induced significant yields of fetal deaths and malformations. However, the incidence of fetal deaths and malformations induced by a dose of pyrabital was significantly higher than that by an equivalent dose of aminopyrine which was contained in pyrabital. When aminopyrine (0.21 mg/g) and barbital (0.09 mg/g) were given in 2 separate injections to pregnant mice, teratogenicity was approximately equal to that by the equivalent dose of pyrabital (0.3 mg/g). Consequently, potent teratogenicity of pyrabital is not caused by the compound, but only by the coexistence of barbital and aminopyrine. Such enhancement effects of barbital may be due to the induction of enzymes responsible for transforming aminopyrine to teratogenic forms, because pretreatment with barbital and phenobarbital similarly enhanced embryotoxicity of aminopyrine.
氨基比林及其与巴比妥的化合物已被用于人类作为止痛和退热药物。一种化合物，吡拉比妥（2分子氨基比林和1分子巴比妥）在妊娠第9、10和11天每日给药，在ICR/Jcl小鼠中产生了显著的胎儿死亡和畸形率。诱导的大多数畸形是脐膨出破裂（腹腔内脏外翻），这与肠旋转不良、腭裂以及尾部异常、手指和脚趾异常有关。氨基比林也诱导了显著的胎儿死亡和畸形率。然而，吡拉比妥剂量诱导的胎儿死亡和畸形发生率显著高于吡拉比妥中所含等效剂量氨基比林诱导的发生率。当将氨基比林（0.21mg/g）和巴比妥（0.09mg/g）分别注射给怀孕小鼠时，致畸性与等效剂量的吡拉比妥（0.3mg/g）大致相当。因此，吡拉比妥的强致畸性不是由该化合物引起的，而是仅由巴比妥和氨基比林共存引起的。巴比妥的这种增强作用可能是由于诱导了负责将氨基比林转化为致畸形式的酶，因为用巴比妥和苯巴比妥预处理同样增强了氨基比林的胚胎毒性。
