Distinction of benzodiazepine agonists from antagonists by photoaffinity labelling of benzodiazepine receptors in vitro

Neurosci Lett. 1982 Jul 20;31(1):65-9. doi: 10.1016/0304-3940(82)90055-6.

Abstract

When membranes of rat cerebellum are exposed to UV light in the presence of flunitrazepam this ligand can be incorporated into one of the assumed 4 benzodiazepine binding sites of the GABA-benzodiazepine receptor complex. This irreversible incorporation of flunitrazepam, in contrast to reversible binding of this substance, leads to conformational changes of the remaining 3 benzodiazepine binding sites which result in a decreased affinity of benzodiazepine agonists, but not of benzodiazepine antagonists. The investigation of the affinity of drugs for [3H]benzodiazepine antagonist binding before and after photoaffinity labelling of benzodiazepine receptors with flunitrazepam can therefore be used as a sensitive and simple test to distinguish between agonists and antagonists in vitro.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / antagonists & inhibitors
  • Anti-Anxiety Agents / metabolism*
  • Binding, Competitive
  • Carbolines / metabolism
  • Cerebellum / drug effects
  • Cerebellum / metabolism*
  • Flunitrazepam / metabolism*
  • Rats
  • Receptors, Cell Surface / metabolism
  • Receptors, Drug / drug effects
  • Receptors, Drug / metabolism*
  • Receptors, GABA-A
  • Ultraviolet Rays

Substances

  • Anti-Anxiety Agents
  • Carbolines
  • Receptors, Cell Surface
  • Receptors, Drug
  • Receptors, GABA-A
  • 1-methyl-beta-carboline-3-carboxylic acid
  • Flunitrazepam