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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
26
|
| pubmed:dateCreated |
1998-2-13
|
| pubmed:abstractText |
A series of N-substituted 3 alpha-[bis(4'-fluorophenyl)methoxy]tropane analogues has been prepared that function as dopamine uptake inhibitors. The N-methylated analogue of this series had a significantly higher affinity for the dopamine transporter than the parent compound, N-methyl-3 alpha- (diphenylmethoxy)tropane (benztropine, Cogentin). Yet like the parent compound, it retained high affinity for muscarinic receptors. A series of N-substituted compounds were prepared from nor-3 alpha-[bis(4'-fluorophenyl)methoxy]tropane via acylation followed by hydride reduction of the amide or by direct alkylation. All compounds containing a basic tropane nitrogen displaced [3H]WIN 35,428 at the dopamine transporter (Ki range = 8.5-634 nM) and blocked dopamine uptake (IC50 range = 10-371 nM) in rat caudate putamen, whereas ligands with a nonbasic nitrogen were virtually inactive. None of the compounds demonstrated high binding affinity at norepinephrine or serotonin transporters. Importantly, a separation of binding affinities for the dopamine transporter versus muscarinic m1 receptors was achieved by substitution of the N-methyl group with other N-alkyl or arylalkyl substituents (eg. n-butyl, allyl, benzyl, 3-phenylpropyl, etc.). Additionally, the most potent and selective analogue in this series at the dopamine transporter, N-(4"-phenyl-n-butyl)-3 alpha-[bis(4'-fluorophenyl)methoxy]tropane analogue failed to substitute for cocaine in rats trained to discriminate cocaine from saline. Potentially, new leads toward the development of a pharmacotherapeutic for cocaine abuse and other disorders affecting the dopamine transporter may be discovered.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/(1R-(exo,exo))-3-(4-fluorophenyl)-8-...,
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/Dopamine Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
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/Receptors, Muscarinic,
http://linkedlifedata.com/resource/pubmed/chemical/Tropanes
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
19
|
| pubmed:volume |
40
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
4329-39
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:9435902-Animals,
pubmed-meshheading:9435902-Binding, Competitive,
pubmed-meshheading:9435902-Brain,
pubmed-meshheading:9435902-Carrier Proteins,
pubmed-meshheading:9435902-Cocaine,
pubmed-meshheading:9435902-Crystallography, X-Ray,
pubmed-meshheading:9435902-Dopamine,
pubmed-meshheading:9435902-Dopamine Plasma Membrane Transport Proteins,
pubmed-meshheading:9435902-Dopamine Uptake Inhibitors,
pubmed-meshheading:9435902-Ligands,
pubmed-meshheading:9435902-Male,
pubmed-meshheading:9435902-Membrane Glycoproteins,
pubmed-meshheading:9435902-Membrane Transport Proteins,
pubmed-meshheading:9435902-Mice,
pubmed-meshheading:9435902-Models, Molecular,
pubmed-meshheading:9435902-Molecular Structure,
pubmed-meshheading:9435902-Motor Activity,
pubmed-meshheading:9435902-Nerve Tissue Proteins,
pubmed-meshheading:9435902-Rats,
pubmed-meshheading:9435902-Receptors, Muscarinic,
pubmed-meshheading:9435902-Structure-Activity Relationship,
pubmed-meshheading:9435902-Tropanes
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Novel N-substituted 3 alpha-[bis(4'-fluorophenyl)methoxy]tropane analogues: selective ligands for the dopamine transporter.
|
| pubmed:affiliation |
Psychobiology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
|