d-ala(2)-mephe(4)-met(0)-ol-enkephalin and Abnormalities--Drug-Induced

Diamorphine hydrochloride, methadone hydrochloride, and the synthetic enkephalin analogue FK 33-824 are potent teratogens for the central nervous system in mouse embryos. They induce the "neurotropic syndrome of malformations," which is restricted to the central nervous system if administered during the critical period of neural tube closure. Pretreatment with corresponding equimolecular doses of the antagonist naloxone hydrochloride applied 30 minutes before treatment with the opiate agonists abolishes the major severe malformations, i.e., exencephaly, craniorachischisis, and brachyury, and reduces the number of cases of kinking of the spinal cord. Dilation of the fourth brain ventricle remains unaffected. It is suggested that the mechanism of interference in the teratogenicity of the opiates by naloxone hydrochloride reported here is based on competition for opiate receptors. In general, these observations are regarded as evidence that the pharmacological affinity of opiate agonists to receptors in the central nervous system is responsible for the malformations caused by them in this system.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Animals; Central Nervous System; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Female; Heroin; Methadone; Mice; Naloxone; Pregnancy; Receptors, Opioid