Benzodiazepine receptor modulation of [35S]TBPS binding to the chloride channel. Noncompetitive inhibition of classical benzodiazepines and competitive inhibition of the partial agonist, CGS 9895, by CGS 8216

Neuropharmacology. 1987 Jul;26(7A):775-8. doi: 10.1016/0028-3908(87)90241-3.

Abstract

Benzodiazepine receptor ligands are known to modulate the binding of [35S]TBPS to the chloride channel via an allosteric action. In the cases of diazepam, zopiclone and CGS 9895, the enhanced binding of [35S]TBPS induced by these benzodiazepine agonists was antagonized by CGS 8216. This antagonism was characterized both by a shift to the right and a decrease in the maximal stimulation, for the dose-response curves of diazepam and zopiclone. In the case of CGS 9895, the maximal response was not decreased. These data indicate that CGS 8216 is a noncompetitive antagonist of classical benzodiazepine receptor agonists but is a competitive inhibitor of the partial agonist, CGS 9895.

MeSH terms

  • Animals
  • Benzodiazepines / antagonists & inhibitors*
  • Benzodiazepines / physiology
  • Bridged Bicyclo Compounds / metabolism*
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Bridged-Ring Compounds / metabolism*
  • Chlorides / metabolism*
  • Ion Channels / metabolism*
  • Pyrazoles / pharmacology*
  • Rats
  • Receptors, GABA-A / physiology*
  • Sulfur Radioisotopes

Substances

  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Bridged-Ring Compounds
  • Chlorides
  • Ion Channels
  • Pyrazoles
  • Receptors, GABA-A
  • Sulfur Radioisotopes
  • Benzodiazepines
  • tert-butylbicyclophosphorothionate
  • 2,5-dihydro-2-(4-methoxyphenyl)-3H-pyrazolo(4,3-c)quinolin-3-one
  • 2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one