Are "peripheral-type" binding sites for benzodiazepines in brain related to the convulsant actions of Ro 5-4864?

Prog Clin Biol Res. 1985:192:197-203.

Abstract

Previous studies have shown that Ro 5-4864 is a potent convulsant. Investigation of a series of compounds structurally related to Ro-4864 revealed a good correlation (r = .93, p less than 0.01) between their potencies as convulsants and their abilities to displace [35S]t-butylbicyclophosphorothionate from sites associated with the chloride ionophore. In contrast, there appears to be no direct relationship between the convulsant potencies of these compounds and their affinities for "peripheral-type" binding sites for benzodiazepines. These data suggest that "peripheral-type" binding sites for benzodiazepines are not directly involved in the convulsant actions of Ro 5-4864 and related compounds nonetheless, several lines of evidence suggest that "peripheral-type" binding sites for benzodiazepines may be indirectly involved in the convulsant properties of Ro 5-4864.

MeSH terms

  • Animals
  • Benzodiazepinones / pharmacology*
  • Binding, Competitive
  • Brain / drug effects
  • Brain / metabolism*
  • Bridged Bicyclo Compounds / metabolism
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Convulsants / pharmacology*
  • Kinetics
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, GABA-A / metabolism*
  • Structure-Activity Relationship

Substances

  • Benzodiazepinones
  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Convulsants
  • Receptors, GABA-A
  • 4'-chlorodiazepam
  • tert-butylbicyclophosphorothionate