Specific inhibition of binding to benzodiazepine receptors by 1,2,3-triazole derivatives

J Pharm Sci. 1992 Jun;81(6):543-5. doi: 10.1002/jps.2600810615.

Abstract

Certain 1,2,3-triazole derivatives were prepared and tested for their ability to displace [3H]diazepam that was bound to bovine brain membrane protein. All the tested compounds are essentially lacking in this ability, except for B.1, which inhibited binding of [3H]diazepam in 50% of the trials at 2.5 microM. The structure of B.1, with a 1,2,3-triazole ring with acidic properties, supports the hypothesis proposed for binding to the benzodiazepine receptor site. Comparison of B.1 with 1,2,3-triazole derivatives bearing a bicyclic substituent in position 1 of the heterocyclic ring suggests that a high steric hindrance increases the affinity of a compound for the benzodiazepine receptor.

MeSH terms

  • Animals
  • Benzodiazepinones / pharmacology
  • Binding, Competitive / drug effects
  • Cattle
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Diazepam / metabolism
  • In Vitro Techniques
  • Protein Binding / drug effects
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / metabolism
  • Triazoles / chemical synthesis
  • Triazoles / pharmacology*

Substances

  • Benzodiazepinones
  • Receptors, GABA-A
  • Triazoles
  • 4'-chlorodiazepam
  • Diazepam