2006
DOI: 10.2174/156802606778249775
View full text |Buy / Rent full text
|
Sign up to set email alerts
|

Abstract: The dopamine transporter (DAT) is a target for the development of pharmacotherapies for a number of central disorders including Parkinson's disease, Alzheimer's disease, schizophrenia, Tourette's syndrome, Lesch-Nyhan disease, attention deficit hyperactivity disorder (ADHD), obesity, depression, and stimulant abuse as well as normal aging. Considerable effort continues to be devoted to the development of new ligands for the DAT. In this review, we present some of the more interesting ligands developed during t… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
4
1

Citation Types

0
69
0

Year Published

2008
2008
2008
2008

Publication Types

Select...
3

Relationship

2
1

Authors

Journals

citations
Cited by 57 publications
(69 citation statements)
references
References 93 publications
(132 reference statements)
0
69
0
Order By: Relevance
“…DA signaling is implicated in schizophrenia, Parkinson's disease and attention deficit hyperactivity disorder, and treatments targeting these disorders modulate dopaminergic neurotransmission (De Oliveira and Juruena, 2006;Runyon and Carroll, 2006;Carlsson et al, 2007). Extracellular DA levels are regulated by the plasma membrane DAT, which removes DA from the synaptic cleft thereby temporally and spatially constraining DA availability.…”
Section: Introductionmentioning
confidence: 99%
“…Although the DAT tolerates ligands having a broad variety of 2β-substituents with little change in the affinity of the ligand, the nature of the substituents has a profound effect on the monoamine transporter selectivity. 16 To obtain analogs with increased metabolic stability, we have replaced the metabolically labile 2β-ester group of the 3β-phenyltropanes by stable bioisosteric heterocyclic groups, which led to several analogs with high-affinity and selectivity for the DAT. 20,24,30,31 Computational analyses of the electrostatic (molecular electrostatic potential), hydrophobic (calculated logP), and steric (substituted volume) properties of these 2β-heterocyclic analogs strongly suggested electrostatic interactions predominately contributed to their DAT binding affinities.…”
Section: Resultsmentioning
confidence: 99%
“…11-19 A large part of our structure-activity relationships (SAR) studies was directed towards modification of the 4'-chloro and 4'-methyl analogs 1c,d. 16 Over the last several years, we have synthesized a large number of 3-phenyltropane analogs and evaluated them for binding at monoamine transporters. We have shown that a variety of 2β-esters, amides, and heterocyclic groups possessing either a 4'-chloro or 4'-methylphenyl group at the 3β-position had high-affinity for the DAT, in some cases, with considerably reduced affinity at the NET and 5-HTT.…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…12, 15-18 One of the most studied classes of DAT inhibitors is the 3-phenyltropanes. 12,15,19,20 The lead compound was 3β-phenyltropane-2β-carboxylic acid methyl ester (2a, Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript.…”
Section: Introductionmentioning
confidence: 99%