Linked Life Data

1396986

Source:http://linkedlifedata.com/resource/pubmed/id/1396986

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
1992-11-13
pubmed:abstractText
Fifty-four compounds structurally related to zimeldine or alaproclate and eight reference substances were examined as inhibitors of the high affinity binding of [3H]paroxetine to rat cerebral cortical membranes as a measure of the affinity of the 5-hydroxytryptamine (5-HT) transporter. None of the compounds had an affinity as high as paroxetine (KD = 0.026 nM). The most potent compound, 3-(4-methoxyphenyl)-1-methyl-3-phenylpropylamine (2) had a 5 times lower affinity than paroxetine. Some other diphenyl-1-methyl-propylamines displayed high affinity, e.g. the 4-bromo (4) and 2-bromo (7) derivatives. The primary amine analogue of zimeldine substituted with an alpha-methyl group (19) had an affinity only slightly less than that of norzimeldine (11) but an almost 100 times higher affinity than that of the unsubstituted primary zimeldine analogue (57). These observations indicate that a methyl group on the alpha-carbon and on the nitrogen both increase the affinity for the [3H]paroxetine binding site. The structure activity relationship for the compounds to inhibit [3H]paroxetine binding was highly significantly correlated to the inhibition of 5-HT uptake in mouse brain slices (P less than 0.01) and to the inhibition of noradrenaline uptake in the same slices (P less than 0.05). QSAR analysis of the zimeldine series of compounds indicates that substitution of halogens of the 2-position of the phenyl ring is unfavourable. The cis configuration promotes higher activity than the trans configuration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
215
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
191-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Inhibition of [3H]paroxetine binding by various serotonin uptake inhibitors: structure-activity relationships.
pubmed:affiliation
Department of Geriatric Medicine, University of Linköping, Sweden.
pubmed:publicationType
Journal Article, In Vitro