Abstract
Four isomeric N-(halophenyl)trozamicol analogues (6a-d) were synthesized and evaluated as potential vesicular acetylcholine transporter (VAChT) ligands. Of the four compounds, N-(3-bromophenyl) trozamicol (6b) and N-(3-iodophenyl)trozamicol (6d) displayed the highest affinity for the VAChT in vitro, whereas the para-substituted compound 6c showed the lowest affinity for this transporter. Tissue distribution studies of N-(3-[125I]iodophenyl)trozamicol ([125I]6d, [125I)IPHT) suggest that the central distribution of the latter is consistent with cholinergic innervation. However, only moderate target-to-background ratios were obtained, suggesting little improvement over the N-(halobenzyl)trozamicols described previously.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholine / metabolism
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Animals
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Binding, Competitive
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Brain / metabolism*
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Carrier Proteins / metabolism*
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Indicators and Reagents
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Iodine Radioisotopes / pharmacokinetics*
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Iodobenzenes / chemical synthesis
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Iodobenzenes / pharmacokinetics*
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Isomerism
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Kinetics
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Ligands
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Male
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Membrane Transport Proteins*
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Molecular Structure
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Piperazines / chemical synthesis
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Piperazines / pharmacokinetics*
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Piperidines / pharmacokinetics
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Rats
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Rats, Wistar
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Receptors, sigma / analysis
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Receptors, sigma / metabolism
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Structure-Activity Relationship
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Tissue Distribution
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Vesicular Acetylcholine Transport Proteins
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Vesicular Transport Proteins*
Substances
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Carrier Proteins
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Indicators and Reagents
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Iodine Radioisotopes
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Iodobenzenes
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Ligands
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Membrane Transport Proteins
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N-(3-iodophenyl)trozamicol
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Piperazines
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Piperidines
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Receptors, sigma
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Slc18a3 protein, rat
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Vesicular Acetylcholine Transport Proteins
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Vesicular Transport Proteins
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vesamicol
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Acetylcholine