Pharmacological characterization of the vesamicol analogue (+)-[(125)I]MIBT in primate brain

Eur J Pharmacol. 1997 Nov 5;338(2):159-69. doi: 10.1016/s0014-2999(97)81944-9.

Abstract

The vesamicol analogue, meta-[(125)I]iodobenzyltrozamicol [(+)-[(125)I]MIBT] was evaluated as a probe for the in vitro labeling of the vesicular acetylcholine transporter in primate brain. In the striatum, (+)-[(125)I]MIBT bound a single high-affinity site with a Kd value of 4.4 +/- 0.7 nM. Competition for (+)-[(125)I]MIBT binding to the striatum by a group of vesamicol analogues displayed a pharmacological profile similar to the rank order of potency previously observed for the vesicular acetylcholine transporter on Torpedo synaptic vesicles. High-affinity binding of (+)-[(125)I]MIBT in the occipital cortex was characterized by a Kd value of 4.6 +/- 1.1 nM. However, the rank order of potency for inhibition of (+)-[(125)I]MIBT binding to the occipital cortex by the same test compounds differed from that observed in the striatum. The results suggest that (+)-[(125)I]MIBT is a reliable probe of the vesicular acetylcholine transporter in primate striatum, but its binding in primate occipital cortex is more complex.

Publication types

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

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Brain Chemistry / drug effects*
  • Carrier Proteins / metabolism*
  • Iodobenzenes* / pharmacokinetics
  • Ligands
  • Macaca mulatta
  • Male
  • Membrane Transport Proteins*
  • Neostriatum / anatomy & histology
  • Neostriatum / metabolism
  • Neuromuscular Depolarizing Agents / metabolism
  • Piperidines* / metabolism
  • Piperidines* / pharmacokinetics
  • Radioligand Assay
  • Synaptic Vesicles / metabolism
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins*

Substances

  • Carrier Proteins
  • Iodobenzenes
  • Ligands
  • Membrane Transport Proteins
  • Neuromuscular Depolarizing Agents
  • Piperidines
  • Vesicular Acetylcholine Transport Proteins
  • Vesicular Transport Proteins
  • (3-iodobenzyl)trozamicol
  • vesamicol
  • Acetylcholine