Quantitative structure-activity studies of pyrethroids: 23. Rate of decrease in sodium tail currents induced by substituted benzyl chrysanthemates and pyrethrates in crayfish giant axons

Abstract

The effects of pyrethroids, meta-substituted benzyl esters of (1 R)- trans-chrysanthemic and (1 R)- trans-( E)-pyrethric acids, on sodium currents were examined with crayfish giant axons perfused internally. The sodium currents were measured with step depolarization under voltage clamp conditions by the sucrose gap method. The compounds decreased the rate of fall in the tail current that was observed upon step repolarization of the membrane. Variations in the potency to decrease the rate of fall (the tail-current potency) were quantitatively analyzed by use of physicochemical and structural parameters of the aromatic substituents and regression analysis. Structural effects were common to both series of compounds. The introduction of substituents with a phenyl group into the benzyl benzene ring was favorable for the activity. The tail-current potency was also governed by steric dimensions of the substituents in terms of STERIMOL parameters. The aromatic substituents had an optimum width for the potency. The shorter the substituents, the higher was the tail-current potency. Variations in the insecticidal potency of chrysanthemates and pyrethrates against American cockroaches were related linearly with the tail-current potency when the transport factors of compounds were separated by use of the hydrophobicity parameter. The higher the tail-current potency, the higher the insecticidal potency.