MALFORMATIONS OF THE CENTRAL NERVOUS-SYSTEM INDUCED BY NEUROTROPIC DRUGS IN MOUSE EMBRYOS
MALFORMATIONS OF THE CENTRAL NERVOUS-SYSTEM INDUCED BY NEUROTROPIC DRUGS IN MOUSE EMBRYOS
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DOI：
10.1111/j.1440-169x.1980.00061.x
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发表时间：
1980-01-01
影响因子：
2.5
通讯作者：
JURAND, A
中科院分区：
文献类型：
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作者：
JURAND, A
在由7种抗抑郁药和抗精神病药[丙咪嗪、地西帕明、曲美帕明、氯丙咪嗪、阿米替林、氯丙嗪、奋乃静]、2种抗焦虑药[利血平、二氮卓]、1种抗惊厥药[氯硝西泮]、3种阿片类药物[二乙酰吗啡、可待因、罂粟碱]和2种合成镇痛药[喷他佐辛、左啡诺]组成的15种神经营养药物样本中，12种对小鼠胚胎具有致畸性，导致中枢神经系统畸形。在妊娠第9天开始时单次注射致畸剂量后，4天后，即，在13天大的胚胎中，诱导的缺陷似乎构成了畸形的复发综合征，其由在相同胚胎中以不同频率单独或组合存在的几种异常组成。这些畸形包括露脑畸形、颅脊柱裂、颈椎和胸腰椎脊髓劈裂、第四脑室脑积水扩张、脊髓Z形扭结和腰椎脊髓积水。给药后的一些药物，branchyurir或anurir与或不腰椎骨髓增生。显然，由于其可能的亲和力，如果在神经管闭合时应用，亲神经性药物对胚胎CNS具有潜在的致畸性，尽管已知这类药物中有不引起任何CNS畸形的药物，并且许多非亲神经性药物确实引起此类畸形。畸形沿着脊柱-脊髓轴的位置可能在一定程度上取决于药物的药理学性质。
Of a sample of 15 neurotropic drugs consisting of 7 antidepressants and antipsychotic [imipramine, desepramine, trimepramine, clomipramine, amytryptiline, chlorpromazine, perphenazine], 2 antianxiety drugs [chlordiazepoxide, diazepom], 1 anticonvulsant [clonozepam], 3 opiates [diamorphine, codeine, papaverine] and 2 synthetic analgesics [pentazocine, levorphonol], 12 were teratogenic for mouse embryos, causing malformations of the CNS. After single injections of the teratogenic dose administered at the very beginning of the 9th day of gestation, 4 days later, i.e., in 13 day old embryos, the induced defects appeared to make up a recurring syndrome of malformations which consists of several abnormalities present in various frequencies individually or in combination in the same embryos. These malformations are exencephaly, craniorachischisis, cervical and thoraco-lumbar myeloschisis, hydrocephalic dilatation of the 4th brain ventricle, Z-shaped kinking of the spinal cord and lumbar hydromyelia. After administration of some of the drugs, branchyury or anury with or without lumbar myeloaplasia were recorded. Apparently, because of their possible affinity, neurotropic drugs are potentially teratogenic for the embryonic CNS if applied at the time of the neural tube closure although it is known that there are drugs in this group which do not cause any CNS malformations and that many non-neurotropic agents do cause such malformations. Position of the malformation along the cerebro-spinal axis may depend to some extent on the pharmacological properties of the drugs.