Design, synthesis, and in vitro pharmacology of new radiolabeled gamma-hydroxybutyric acid analogues including photolabile analogues with irreversible binding to the high-affinity gamma-hydroxybutyric acid binding sites

J Med Chem. 2010 Sep 9;53(17):6506-10. doi: 10.1021/jm1006325.

Abstract

Gamma-hydroxybutyric acid (GHB) is a psychotropic compound endogenous to the brain. Despite its potential physiological significance, the complete molecular mechanisms of action remain unexplained. To facilitate the isolation and identification of the high-affinity GHB binding site, we herein report the design and synthesis of the first (125)I-labeled radioligands in the field, one of which contains a photoaffinity label which enables it to bind irreversibly to the high-affinity GHB binding sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azides / chemical synthesis*
  • Azides / chemistry
  • Azides / metabolism
  • Binding Sites
  • Binding, Competitive
  • Cerebral Cortex / metabolism
  • Drug Design
  • Hydroxybutyrates / chemical synthesis*
  • Hydroxybutyrates / chemistry
  • Hydroxybutyrates / metabolism
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Ligands
  • Light
  • Photoaffinity Labels / chemical synthesis*
  • Photoaffinity Labels / chemistry
  • Photoaffinity Labels / metabolism
  • Protein Binding
  • Radioligand Assay
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Azides
  • Hydroxybutyrates
  • Iodine Radioisotopes
  • Ligands
  • Photoaffinity Labels
  • 4-hydroxybutyric acid