Cross-resistance with dieldrin of a novel tricyclic dinitrile GABA receptor antagonist

Br J Pharmacol. 1999 Jul;127(6):1305-7. doi: 10.1038/sj.bjp.0702663.

Abstract

A novel tricyclic dinitrile, KN244, blocked the wild-type (dieldrin-sensitive) homo-oligomeric gamma-aminobutyric acid (GABA)-gated chloride channel of Drosophila melanogaster expressed in Xenopus oocytes. Sensitivity to the block by KN244 of the response to 30 microM GABA (IC50=41.6 nM, wild-type RDLac) was reduced abut 100 fold (IC50=4.5 microM) in the dieldrin-resistant (RDLacA302S) form of RDL.

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds / pharmacology*
  • Chloride Channels / antagonists & inhibitors
  • Dieldrin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drosophila melanogaster
  • GABA Antagonists / pharmacology*
  • Insecticide Resistance
  • Insecticides / pharmacology*
  • Membrane Potentials / drug effects
  • Nitriles / pharmacology*
  • Oocytes / drug effects
  • Oocytes / physiology
  • Receptors, GABA / drug effects*
  • Xenopus
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Bridged Bicyclo Compounds
  • Chloride Channels
  • GABA Antagonists
  • Insecticides
  • KN 244
  • Nitriles
  • Receptors, GABA
  • gamma-Aminobutyric Acid
  • Dieldrin