Teratogenic activity of methadone hydrochloride in mouse and chick embryos

Abstract

Teratogenic activity of methadone HCl (Physeptone, Burroughs Wellcome and Co.) was tested on inbred JBT/Jd and outbred Q strain mouse embryos and on chick embryos. 22–24 mg/kg injected subcutaneously on the 9th day of pregnancy caused by the 13th day exencephaly in 56 out of 479 JBT/Jd embryos but after 32 mg/kg only in 1 out of 220 of the Q strain. Some affected JBT/Jd embryos showed also rachischisis in the cervical area. The second abnormality shown by the embryos of both strains is Z-shaped kinkage of the spinal cord. In explanted chick embryos cultured in vitro as well as in embryos treated in ovo metha-done causes non-closure of the neural tube with extensive necrosis of the neural plate cells in the cephalic region. The results of this study indicate that methadone, which is a neutropic drug, has an embryo-toxic activity directed against the developing central nervous system.