Pyrethroid insecticides: stereospecific allosteric interaction with the batrachotoxinin-A benzoate binding site of mammalian voltage-sensitive sodium channels

Mol Pharmacol. 1988 Jul;34(1):54-9.

Abstract

Pyrethroid insecticides are synthetic neurotoxins patterned after the naturally occurring pyrethrins. Their mechanism of action is thought to involve effects primarily at the voltage-sensitive sodium channel of both insect and mammalian neurons, although recent studies have raised the possibility that these compounds may also act at the gamma-aminobutyric acid receptor-chloride ionophore complex. Here we show that active pyrethroids of the alpha-cyano-3-phenoxybenzyl class allosterically enhance the binding of [3H]batrachotoxinin-A 20-alpha-benzoate to voltage-sensitive sodium channels of rat brain in a dose-dependent and stereospecific manner. Comparison of the rank order of potency for enhancement of [3H]batrachotoxinin-A 20-alpha-benzoate binding and insecticidal activity in a series of toxic stereoisomers of cypermethrin, representative of the class, reveals a correlation between the two measures. These results support a sodium channel site model for pyrethroid action and suggest a useful and practical method to help evaluate the relationship between effects at the sodium channel and insecticidal potency for members of this class of compounds.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allosteric Regulation
  • Animals
  • Batrachotoxins / metabolism
  • DDT / pharmacology
  • In Vitro Techniques
  • Insecticides / pharmacology
  • Ion Channels / drug effects*
  • Pyrethrins / pharmacology*
  • Rats
  • Receptors, Cholinergic / drug effects*
  • Sodium / metabolism*
  • Sodium Channels*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Batrachotoxins
  • Insecticides
  • Ion Channels
  • Pyrethrins
  • Receptors, Cholinergic
  • Sodium Channels
  • batrachotoxin receptor
  • Sodium
  • DDT