Linked Life Data

1361690

Source:http://linkedlifedata.com/resource/pubmed/id/1361690

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1993-1-26
pubmed:abstractText
A qualitative assessment of developmental toxicity within a series of 12 structurally related compounds, 11 of which were active dopamine mimetics and one was inactive, was conducted in rats treated orally by gavage during the major period of organogenesis. Doses were chosen where possible to be equipotent in terms of pharmacological activity. The series was typified by the compound BRL 16644 (2-[[3,4-dihydro-2,2-dimethyl-4-[3-(trifluoromethyl)phenyl]- 2H-1-benzopyran-7-yl]oxy]-N,N-dimethyl-ethanamine: Chemical Abstracts No. 59257-24-8). Five of these compounds were clearly teratogenic producing specific abnormalities typified by anasarca, brachygnathia and cleft palate. Similar levels of maternal toxicity, particularly stereotypic behaviour, and foetotoxicity were seen in both teratogenic and non-teratogenic compounds suggesting that neither maternal nor foetotoxicity plays a role in the aetiology of the abnormalities. Four of the teratogenic compounds contained a trifluoromethyl group in the 4-phenyl ring and, within this series of compounds, substitution with this group appears to confer teratogenicity. Although equipotent doses were used this only pertained to the adult and as only limited pharmacokinetic data were available, including the extent of placental transfer, the influence of this group is not clear. Investigations have been undertaken to relate the teratogenic potential of these compounds to a number of their chemical descriptors, including electronic, steric, quantum chemical and hydrophobicity parameters, to try and clarify the influence of the trifluoromethyl group.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0300-483X
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
197-207
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
A qualitative assessment of developmental toxicity within a series of structurally related dopamine mimetics.
pubmed:affiliation
SmithKline Beecham Pharmaceuticals, Welwyn, Herts, UK.
pubmed:publicationType
Journal Article