Enhancement effects of barbital on the teratogenicity of aminopyrine.

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.