Abstract
In our continued exploration of trishomocubane derivatives with central nervous system (CNS) activity, N-arylalkyl-8-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecanes (10-13) displaying affinity for the sigma (σ) receptor were also found, in several cases, to interact with the dopamine transporter (DAT). Compound 12 was identified as the first trishomocubane-derived high affinity DAT ligand (K(i) = 1.2 nM), with greater than 8300-fold selectivity over the monoamine transporters NET and SERT, and only low to moderate affinity for σ(1) and σ(2) receptors.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Alkanes / chemical synthesis
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Alkanes / chemistry*
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Alkanes / pharmacology
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Benzylamines / chemical synthesis
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Benzylamines / chemistry*
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Benzylamines / pharmacology
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Bridged-Ring Compounds / chemical synthesis
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Bridged-Ring Compounds / chemistry*
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Bridged-Ring Compounds / pharmacology
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Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors*
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Dopamine Plasma Membrane Transport Proteins / metabolism
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Dopamine Uptake Inhibitors / chemical synthesis
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Dopamine Uptake Inhibitors / chemistry*
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Dopamine Uptake Inhibitors / pharmacology
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Ligands
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Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors
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Norepinephrine Plasma Membrane Transport Proteins / metabolism
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Protein Binding
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Receptors, sigma / antagonists & inhibitors
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Receptors, sigma / metabolism
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Serotonin Plasma Membrane Transport Proteins / chemistry
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Serotonin Plasma Membrane Transport Proteins / metabolism
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Structure-Activity Relationship
Substances
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Alkanes
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Benzylamines
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Bridged-Ring Compounds
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Dopamine Plasma Membrane Transport Proteins
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Dopamine Uptake Inhibitors
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Ligands
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Norepinephrine Plasma Membrane Transport Proteins
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Receptors, sigma
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Serotonin Plasma Membrane Transport Proteins
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undecane