Audiogenic seizures in DBA/2 mice discriminate sensitively between low efficacy benzodiazepine receptor agonists and inverse agonists

Life Sci. 1983 Jul 25;33(4):393-9. doi: 10.1016/s0024-3205(83)80014-9.

Abstract

In experiments with audiogenic seizures in DBA/2 mice, we observed that several socalled benzodiazepine receptor antagonists exhibited either anticonvulsive (Ro 15-1788, PrCC) or proconvulsive (FG 7142, beta-CCE, CGS 8216) effects at high receptor occupancy (17-85%), as compared to benzodiazepines and DMCM which had anticonvulsive and proconvulsive actions, respectively, at very low receptor occupancy (less than 10%). Sensitive distinction between benzodiazepine receptor ligands with low anticonvulsive efficacy (partial agonists) and ligands with low proconvulsive, and maybe anxiogenic, efficacy (partial inverse agonists) can thus be obtained in sound seizure susceptible mice.

Publication types

  • Comparative Study

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Anticonvulsants / pharmacology
  • Benzodiazepines / antagonists & inhibitors*
  • Benzodiazepines / pharmacology
  • Benzodiazepinones / pharmacology
  • Carbolines / pharmacology
  • Convulsants / pharmacology
  • Flumazenil
  • Male
  • Mice
  • Mice, Inbred DBA
  • Pyrazoles / pharmacology
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / physiology*
  • Receptors, GABA-A
  • Seizures / physiopathology*

Substances

  • Anticonvulsants
  • Benzodiazepinones
  • Carbolines
  • Convulsants
  • Pyrazoles
  • Receptors, Cell Surface
  • Receptors, GABA-A
  • Benzodiazepines
  • Flumazenil
  • 2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one