Cholinomimetic teratogens. VI. The interaction of cholinomimetic teratogens with the antimalarial drugs chloroquine and chlorguanide.

A typical syndrome of short and crooked neck together with muscular hytoplasia of the legs occurs with low incidence in chicken embryos following injection into the egg at 24 hours of incubation of the antimalarial drug chloroquine; but treatment at later stages does not have similar effects. When, however chloroquine was used in addition to carbachol or neostigmine at 96 hours of incubation the malformations caused by the two cholinomimetic compounds, i.e., carbachol and neostigmine, occurred with greatly increased frequency and tended also to be exaggerated in expression. Chlorguanide, another antimalarial drug, when used as additive, reduced the teratogenic effects of such compounds as decamethonium and neostigmine. It appears that the neuromuscular pathways to teratogenicity are for carbachol and neostigmine and for chloroquine clearly related, if at different levels of expressivity.