Incidence and potentiation of external and internal fetal anomalies resulting from chlordiazepoxide and amitriptyline alone and in combination. 1984

B K Beyer, and M S Guram, and W F Geber

The teratogenic potential of a combination of chlordiazepoxide (Cdz) and amitriptyline (Amt) was examined with regard to both internal and external anomalies. Timed pregnant golden hamsters were given a single intraperitoneal injection on day 8 of gestation of one of the following: chlordiazepoxide hydrochloride (28.5 mg/kg), amitriptyline hydrochloride (70.3 mg/kg), Cdz-Amt combination (28.5 mg/kg Cdz + 70.3 mg/kg Amt, in order to retain the 1:2.5 dose ratio utilized in a clinically-used preparation of these agents), or saline vehicle (control). Fetuses were recovered on gestation day 15 following maternal sacrifice. Cranial malformations were analyzed in Bouin's-fixed fetuses by making 1-mm coronal sections through each head, whereas visceral anomalies were examined following general dissection of each body. Amt alone produced a significant (P less than 0.05) incidence of bent tail and encephalocele, whereas Cdz significantly (P less than 0.05) altered the male:female ratio of surviving fetuses when compared with saline-injected controls. The Cdz-Amt combination caused significant increases in cranial malformations, open eye, bent tail, abnormal lung, and urogenital anomalies. The teratogenic effects of potentiation between the components of this combination are discussed in terms of external and internal malformations.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D008647 Mesocricetus A genus in the order Rodentia and family Cricetidae. One species, Mesocricetus auratus or golden hamster is widely used in biomedical research. Hamsters, Golden,Hamsters, Golden Syrian,Hamsters, Syrian,Mesocricetus auratus,Syrian Golden Hamster,Syrian Hamster,Golden Hamster,Golden Hamster, Syrian,Golden Hamsters,Golden Syrian Hamsters,Hamster, Golden,Hamster, Syrian,Hamster, Syrian Golden,Syrian Hamsters
D009436 Neural Tube Defects Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure. (From Joynt, Clinical Neurology, 1992, Ch55, pp31-41) Craniorachischisis,Developmental Defects, Neural Tube,Diastematomyelia,Exencephaly,Neurenteric Cyst,Spinal Cord Myelodysplasia,Tethered Cord Syndrome,Acrania,Developmental Neural Tube Defects,Iniencephaly,Neural Tube Developmental Defects,Neuroenteric Cyst,Occult Spinal Dysraphism,Occult Spinal Dysraphism Sequence,Tethered Spinal Cord Syndrome,Acranias,Craniorachischises,Cyst, Neurenteric,Cyst, Neuroenteric,Cysts, Neurenteric,Cysts, Neuroenteric,Defect, Neural Tube,Defects, Neural Tube,Diastematomyelias,Dysraphism, Occult Spinal,Dysraphisms, Occult Spinal,Exencephalies,Iniencephalies,Myelodysplasia, Spinal Cord,Myelodysplasias, Spinal Cord,Neural Tube Defect,Neurenteric Cysts,Neuroenteric Cysts,Occult Spinal Dysraphisms,Spinal Cord Myelodysplasias,Spinal Dysraphism, Occult,Spinal Dysraphisms, Occult,Tethered Cord Syndromes
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002707 Chlordiazepoxide An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawal. Methaminodiazepoxide,7-Chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide,7-Chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-amine 4-oxide,Chlordiazepoxide Hydrobromide,Chlordiazepoxide Hydrochloride,Chlordiazepoxide Monohydrochloride,Chlordiazepoxide Perchlorate,Chlozepid,Elenium,Librium,7 Chloro 2 methylamino 5 phenyl 3H 1,4 benzodiazepine 4 oxide,7 Chloro N methyl 5 phenyl 3H 1,4 benzodiazepin 2 amine 4 oxide,Hydrobromide, Chlordiazepoxide,Hydrochloride, Chlordiazepoxide,Monohydrochloride, Chlordiazepoxide,Perchlorate, Chlordiazepoxide
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004677 Encephalocele Brain tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. Frontal Encephalocele,Hernia, Cerebral,Occipital Encephalocele,Acquired Encephalocele,Bifid Cranium,Cephalocele,Cerebellar Hernia,Cerebellar Herniation,Cranial Meningoencephalocele,Craniocele,Cranium Bifidum,Encephalocele, Acquired,Encephalocele, Frontal,Encephalocele, Occipital,Encephalocele, Sincipital,Notoencephalocele,Sincipital Encephalocele,Tonsillar Hernia,Tonsillar Herniation,Acquired Encephaloceles,Bifid Craniums,Bifidum, Cranium,Bifidums, Cranium,Cephaloceles,Cerebellar Hernias,Cerebellar Herniations,Cerebral Hernia,Cerebral Hernias,Cranial Meningoencephaloceles,Cranioceles,Cranium Bifidums,Cranium, Bifid,Craniums, Bifid,Encephaloceles,Encephaloceles, Acquired,Encephaloceles, Frontal,Encephaloceles, Occipital,Encephaloceles, Sincipital,Frontal Encephaloceles,Hernia, Cerebellar,Hernia, Tonsillar,Hernias, Cerebellar,Hernias, Cerebral,Hernias, Tonsillar,Herniation, Cerebellar,Herniation, Tonsillar,Herniations, Cerebellar,Herniations, Tonsillar,Meningoencephalocele, Cranial,Meningoencephaloceles, Cranial,Notoencephaloceles,Occipital Encephaloceles,Sincipital Encephaloceles,Tonsillar Hernias,Tonsillar Herniations
D005124 Eye Abnormalities Congenital absence of or defects in structures of the eye; may also be hereditary. Abnormalities, Eye,Abnormality, Eye,Eye Abnormality

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