Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1996-2-28
|
| pubmed:abstractText |
This report concerns the synthesis and chemical characterization of novel series of N-substituted 2 beta-carbomethoxy-3 beta-(4'-iodophenyl)tropane (beta-CIT, 2) analogs and their neuropharmacological evaluation for affinity at dopamine (DAT), serotonin (5-HTT), and norepinephrine membrane transporters in rat brain tissue. N-Substituted analogs of beta-CIT with a 2 beta-carbomethoxy ester moiety showed lower DAT affinity than beta-CIT for the DAT, and some were more selective for the 5-HTT over the DAT. 2 beta-Carbomethoxy(iodophenyl)nortropane analogs of beta-CIT with the N-substituents difluoroethyl, mesoxypropyl, iodopropyl, and methylpropionyl all yielded > 10-fold lower DAT affinity than beta-CIT itself, whereas the N-(fluoropropyl)-2 beta- isopropyl ester analog (1) of beta-CIT exceeded beta-CIT (2, an N-methyl-2 beta-carbomethoxy ester) in DAT affinity. Several N-haloalkyl-substituted beta-CIT analogs yielded high 5-HTT affinity (Ki < 0.6 nM), ranking: N-fluoropropyl (5) > N-chloropropyl (4) > or = N-bromopropyl (3) > beta-CIT (2) > N-3'-phtalimidopropyl (11), with particularly high (ca. 30-fold) 5-HTT-over-DAT selectivity found in the N-fluoropropyl (5) and N-fluoroethyl (6) compounds, compared to only 3.o-fold 5-HTT selectivity in beta-CIT itself. Highly 5-HTT selective agents such as 5 and 6 may be useful as brain-imaging ligands for serotonin neurons or as mood-elevating drugs, while the high affinity and selectivity for the DA transporter found in N-(fluoropropyl)-2 beta-(carboxyisopropyl)-3 beta-(4'-iodophenyl)-nortropane (1) and N-(fluoropropyl)-2 beta-carboxymethoxy-3 bet-(4'-iodophenyl)nortropane (FP-beta-CIT, 5) support their use as improved markers for DA neurons.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| 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/Molecular Probes,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RTI 55,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Plasma Membrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Slc6a3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Slc6a4 protein, rat
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
19
|
| pubmed:volume |
39
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
543-8
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8558525-Animals,
pubmed-meshheading:8558525-Binding Sites,
pubmed-meshheading:8558525-Carrier Proteins,
pubmed-meshheading:8558525-Cocaine,
pubmed-meshheading:8558525-Dopamine,
pubmed-meshheading:8558525-Dopamine Plasma Membrane Transport Proteins,
pubmed-meshheading:8558525-Magnetic Resonance Spectroscopy,
pubmed-meshheading:8558525-Membrane Glycoproteins,
pubmed-meshheading:8558525-Membrane Transport Proteins,
pubmed-meshheading:8558525-Molecular Probes,
pubmed-meshheading:8558525-Nerve Tissue Proteins,
pubmed-meshheading:8558525-Prosencephalon,
pubmed-meshheading:8558525-Radioligand Assay,
pubmed-meshheading:8558525-Rats,
pubmed-meshheading:8558525-Serotonin,
pubmed-meshheading:8558525-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:8558525-Spectrometry, Mass, Fast Atom Bombardment
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
N-substituted analogs of 2 beta-carbomethoxy-3 beta- (4'-iodophenyl)tropane (beta-CIT) with selective affinity to dopamine or serotonin transporters in rat forebrain.
|
| pubmed:affiliation |
Research Biochemicals International (RBI), Natick, Massachusetts 01760, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|