N-(3-Iodophenyl)trozamicol (IPHT) and related inhibitors of vesicular acetylcholine transport: synthesis and preliminary biological characterization

Nucl Med Biol. 1999 Aug;26(6):609-17. doi: 10.1016/s0969-8051(99)00013-x.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Binding, Competitive
  • Brain / metabolism*
  • Carrier Proteins / metabolism*
  • Indicators and Reagents
  • Iodine Radioisotopes / pharmacokinetics*
  • Iodobenzenes / chemical synthesis
  • Iodobenzenes / pharmacokinetics*
  • Isomerism
  • Kinetics
  • Ligands
  • Male
  • Membrane Transport Proteins*
  • Molecular Structure
  • Piperazines / chemical synthesis
  • Piperazines / pharmacokinetics*
  • Piperidines / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Receptors, sigma / analysis
  • Receptors, sigma / metabolism
  • Structure-Activity Relationship
  • Tissue Distribution
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins*

Substances

  • Carrier Proteins
  • Indicators and Reagents
  • Iodine Radioisotopes
  • Iodobenzenes
  • Ligands
  • Membrane Transport Proteins
  • N-(3-iodophenyl)trozamicol
  • Piperazines
  • Piperidines
  • Receptors, sigma
  • Slc18a3 protein, rat
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins
  • vesamicol
  • Acetylcholine