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Abstract Chlorcyclizine and structurally related drugs induce a high incidence of cleft palate and skeletal malformations in fetal rats. We have shown previously that these teratogens bind tightly and reversibly to chondroitin sulfate of cartilage and compete with calcium for binding. Experiments reported here demonstrate that co‐administration of calcium chelating agents with chlorcyclizine significantly increases both the frequency of malformations and retention of 14 C chlorcyclizine by embryos. Retention of radioactive teratogen by embryos is inverse to retention of 45 Ca calcalcium. These findings suggest that drug binding to embryonic glycosaminoglycans is involved in the pathogenesis of malformations produced by chlorcyclizine.
Wilk et al. (Sun,) studied this question.