Specific inhibition of benzodiazepine receptor binding by some N-(indol-3-ylglyoxylyl)amino acid derivatives: stereoselective interactions

J Med Chem. 1989 Dec;32(12):2514-8. doi: 10.1021/jm00132a004.

Abstract

Several optically active N-(indol-3-ylglyoxylyl)amino acid derivatives were synthesized and tested for [3H]flunitrazepam displacing activity in bovine brain membranes. IC50 values were measured and revealed that the D form of the amino acid moiety of the compounds was more potent than both the L form and racemic form, suggesting a key role of the amino acid stereochemistry on the affinity to the benzodiazepine receptors. GABA ratio and proconvulsant/convulsant data reported for the most active compounds reveal they behave as inverse agonists at the benzodiazepine receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemical synthesis
  • Amino Acids / pharmacology*
  • Animals
  • Cattle
  • Cerebral Cortex / metabolism
  • Chemical Phenomena
  • Chemistry
  • Indoles / chemical synthesis
  • Indoles / pharmacology*
  • Molecular Conformation
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / metabolism
  • Stereoisomerism

Substances

  • Amino Acids
  • Indoles
  • Receptors, GABA-A