Linked Life Data

7830281

Source:http://linkedlifedata.com/resource/pubmed/id/7830281

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-2-23
pubmed:abstractText
Several 2 beta-carboxylic acid ester and amide analogues of cocaine and of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid were prepared. The binding affinities of these compounds, and of some previously prepared analogues, at the dopamine (DA), norepinephrine (NE), and serotonin (5-HT) transporters were determined. The phenyl esters of 3 beta-(4'-methylphenyl)- and 3 beta-(4'-chlorophenyl)tropane-2 beta-carboxylic acid are highly potent and highly selective for the DA transporter. The isopropyl esters of 3 beta-(4'-chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid also possess high DA affinity and show significant DA transporter selectivity. Similarly, the phenyl and isopropyl ester analogues of cocaine are much more selective for the DA transporter than cocaine. Tertiary amide analogues of cocaine and of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acids are more potent inhibitors of radioligand binding at the DA transporter than the primary and secondary amide analogues. In particular, 3 beta-(4'-chlorophenyl)tropane-2 beta-N-morpholinocarboxamide as well as the 3 beta-(4'-chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-N- pyrrolidinocarboxamides possess high affinity and selectivity for the DA transporter. The N,N-dimethylamide cocaine analogue is the most selective cocaine amide derivative for the DA transporter. High correlation between the inhibition of radioligand binding and inhibition of uptake at the DA, NE, and 5-HT transporter was found for a selected group of analogues. Within this group, one compound, the isopropyl ester of 3 beta-(4'-iodophenyl)-tropane-2 beta-carboxylic acid, was found to be more potent in the inhibition of radioligand binding than in the inhibition of DA uptake. Taken together with its high potency and selectivity at the DA transporter, this suggests that this compound may be a lead in the development of a cocaine antagonist.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
379-88
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:7830281-Amides, pubmed-meshheading:7830281-Animals, pubmed-meshheading:7830281-Carboxylic Acids, pubmed-meshheading:7830281-Carrier Proteins, pubmed-meshheading:7830281-Cerebral Cortex, pubmed-meshheading:7830281-Chemistry, Physical, pubmed-meshheading:7830281-Cocaine, pubmed-meshheading:7830281-Corpus Striatum, pubmed-meshheading:7830281-Dopamine, pubmed-meshheading:7830281-Dopamine Plasma Membrane Transport Proteins, pubmed-meshheading:7830281-Esters, pubmed-meshheading:7830281-Membrane Glycoproteins, pubmed-meshheading:7830281-Membrane Transport Proteins, pubmed-meshheading:7830281-Mesencephalon, pubmed-meshheading:7830281-Nerve Tissue Proteins, pubmed-meshheading:7830281-Norepinephrine, pubmed-meshheading:7830281-Physicochemical Phenomena, pubmed-meshheading:7830281-Radioligand Assay, pubmed-meshheading:7830281-Rats, pubmed-meshheading:7830281-Rats, Sprague-Dawley, pubmed-meshheading:7830281-Serotonin
pubmed:year
1995
pubmed:articleTitle
Cocaine and 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid ester and amide analogues. New high-affinity and selective compounds for the dopamine transporter.
pubmed:affiliation
Research Triangle Institute, Research Triangle Park, North Carolina 27709.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.