title: N-(3-Iodophenyl)trozamicol (IPHT) and related inhibitors of vesicular acetylcholine transport: synthesis and preliminary biological characterization.
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.
authors.affiliation: Department of Radiology, University of Minnesota, Minneapolis 55455, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Khare
authors.forename: R B
authors.initials: RB
authors.lastname: Langason
authors.forename: S M
authors.initials: SM
authors.lastname: Parsons
authors.forename: R H
authors.initials: RH
authors.lastname: Mach
authors.forename: S M
authors.initials: SM
authors.lastname: Efange
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D007462:Iodobenzenes / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007536:Isomerism; D007700:Kinetics; D008024:Ligands; D008297:Male; D026901:Membrane Transport Proteins; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D010880:Piperidines / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000032:analysis / Q000378:metabolism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008024:Ligands; D026901:Membrane Transport Proteins; C402164:N-(3-iodophenyl)trozamicol; D010879:Piperazines; D010880:Piperidines; D017480:Receptors, sigma; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; C006189:vesamicol; D000109:Acetylcholine