| Prenatal toxicity studies in rats and rabbits with the calcium channel blocker diproteverine. | |
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MedLine Citation:
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PMID: 8998385 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In prenatal toxicity studies, diproteverine, a calcium channel blocker with demonstrated antianginal properties, produced an unusual pattern of digital, heart, tail, and vertebral defects in rat fetuses from mothers treated during the major period of organogenesis, but only a very low incidence of heart abnormalities was seen in the rabbit. Heart changes were rarely seen in association with digital defects. The findings were consistent with those seen with other calcium channel blockers and add weight to the suggestion of Danielsson and colleagues (5) that digital malformations are a class effect for this type of compound, the effects being related to reduced uteroplacental blood flow. In addition, it is proposed that cardiovascular malformations are also a class response with calcium channel blockers. The distribution of fetal death and hemorrhages and the varying association between cardiovascular, digital, and tail abnormalities seen in the rat with increasing doses of diproteverine fits the pattern of changes reported following hypoxia in the chick embryo. Reduced uteroplacental blood flow with resultant embryonic hypoxia secondary to pharmacologic action is considered a probable mechanism of action for the induction of abnormalities produced by calcium channel blockers. |
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Authors:
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J E Ridings; A K Palmer; E J Davidson; J A Baldwin |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Reproductive toxicology (Elmsford, N.Y.) Volume: 10 ISSN: 0890-6238 ISO Abbreviation: Reprod. Toxicol. Publication Date: 1996 Jan-Feb |
Date Detail:
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Created Date: 1997-01-17 Completed Date: 1997-01-17 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 8803591 Medline TA: Reprod Toxicol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 43-9 Citation Subset: IM |
Affiliation:
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Smithkline Beecham Pharmaceuticals, Toxicology Department UK, Welwyn, Hertfordshire, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Multiple
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chemically induced Animals Anoxia / chemically induced Body Weight / drug effects Calcium Channel Blockers / administration & dosage, toxicity* Embryonic and Fetal Development / drug effects* Extremities / embryology Female Fetal Resorption / chemically induced Heart Defects, Congenital / chemically induced Isoquinolines / administration & dosage, toxicity* Limb Deformities, Congenital Placental Circulation / drug effects Pregnancy Pregnancy, Animal / drug effects* Prenatal Exposure Delayed Effects Rabbits Rats Rats, Sprague-Dawley Spine / abnormalities, drug effects, embryology |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channel Blockers; 0/Isoquinolines; 69373-95-1/diproteverine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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