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rdf:type |
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lifeskim:mentions |
umls-concept:C0010097,
umls-concept:C0013030,
umls-concept:C0016733,
umls-concept:C0028823,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0162512,
umls-concept:C0205145,
umls-concept:C0220781,
umls-concept:C1159719,
umls-concept:C1167622,
umls-concept:C1510827,
umls-concept:C1883254
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pubmed:issue |
9
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pubmed:dateCreated |
1994-6-9
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pubmed:abstractText |
A novel entry to tropane analogs of cocaine was developed on the basis of the reaction of rhodium-stabilized vinylcarbenoids with pyrroles. These analogs were tested in binding to dopamine and serotonin (5-HT) transporters in membranes from rat striatum and frontal cortex. In all the analogs, the aryl group at the 3-position was directly bound to the tropane ring (as in WIN-35,428), and methyl or ethyl ketone moieties were present at the 2-position instead of the typical ester group. The series of analogs containing a 2-naphthyl group at the 3-position were most potent, with Ki values < 1 nM in binding to both dopamine and 5-HT transporters. Although the unsubstituted 2-naphthyl analog was nonselective at dopamine and 5-HT transport sites, other compounds were selective for either site. In general, compounds with relatively small substituents on the aromatic moiety (such as p-methyl or p-fluoro) were relatively selective for the dopamine transporters, while a p-isopropylphenyl derivative was selective for the 5-HT transport sites. This latter compound represents the first N-methyltropane derivative specific for 5-HT transporters. Resolution of two of the most significant analogs was achieved by HPLC on a chiral stationary phase; the active enantiomer of a 2-naphthyl analog exhibited Ki values of < 0.1 nM at both dopamine and 5-HT transporter sites.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cocaine,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Plasma Membrane Transport...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles,
http://linkedlifedata.com/resource/pubmed/chemical/RTI 55,
http://linkedlifedata.com/resource/pubmed/chemical/Rhodium,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Plasma Membrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Slc6a4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
29
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pubmed:volume |
37
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1262-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8176704-Animals,
pubmed-meshheading:8176704-Binding, Competitive,
pubmed-meshheading:8176704-Binding Sites,
pubmed-meshheading:8176704-Carrier Proteins,
pubmed-meshheading:8176704-Cocaine,
pubmed-meshheading:8176704-Corpus Striatum,
pubmed-meshheading:8176704-Dopamine Plasma Membrane Transport Proteins,
pubmed-meshheading:8176704-Frontal Lobe,
pubmed-meshheading:8176704-Male,
pubmed-meshheading:8176704-Membrane Glycoproteins,
pubmed-meshheading:8176704-Membrane Transport Proteins,
pubmed-meshheading:8176704-Molecular Structure,
pubmed-meshheading:8176704-Nerve Tissue Proteins,
pubmed-meshheading:8176704-Pyrroles,
pubmed-meshheading:8176704-Rats,
pubmed-meshheading:8176704-Rats, Sprague-Dawley,
pubmed-meshheading:8176704-Rhodium,
pubmed-meshheading:8176704-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:8176704-Structure-Activity Relationship,
pubmed-meshheading:8176704-Tritium
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pubmed:year |
1994
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pubmed:articleTitle |
Synthesis of 2 beta-acyl-3 beta-aryl-8-azabicyclo[3.2.1]octanes and their binding affinities at dopamine and serotonin transport sites in rat striatum and frontal cortex.
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pubmed:affiliation |
Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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