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.