Selective cytostatic and neurotoxic effects of avermectins and activation of the GABAalpha receptors

Biosci Rep. 1999 Dec;19(6):535-46. doi: 10.1023/a:1020262811459.

Abstract

A natural avermectin complex, aversectin C, was shown to be capable of exerting selective cytostatic and neurotoxic effects on mammalian cells. Specifically, it killed proliferating neuroblastoma B103 cells but was non-toxic for differentiated cells of this culture. The antiproliferation action of aversectin C was not inhibited by bicuculline or picrotoxin, antagonists of the GABAalpha receptors, and was partly due to the action of avermectin A1, a component of aversectin C. Aversectin C irreversibly suppressed activity of 60% neurons in medial septal slices of the rat brain. More than 55% of them were the GABAalpha- and B1-sensitive neurons whereas the rest, about 45% neurons, were the GABAalpha-insensitive and the neurotoxic effect of aversectin C was caused mainly by the B2 component.

MeSH terms

  • Animals
  • Bicuculline / pharmacology
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • Ivermectin / analogs & derivatives*
  • Ivermectin / pharmacology
  • Male
  • Neuroblastoma / drug therapy
  • Neurons / drug effects*
  • Neurotoxins / pharmacology*
  • Pentobarbital / pharmacology
  • Picrotoxin
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / drug effects*
  • Septal Nuclei / drug effects
  • Tumor Cells, Cultured

Substances

  • GABA Agonists
  • GABA Antagonists
  • Neurotoxins
  • Receptors, GABA-A
  • Picrotoxin
  • abamectin
  • Ivermectin
  • avermectin
  • Pentobarbital
  • Bicuculline