Quantitative structure-activity studies of pyrethroids: Physicochemical properties and the rate of development of the residual and tail sodium currents in crayfish giant axon

Abstract

The effects of 28 pyrethroids including variously substituted benzyl chrysanthemates and pyrethrates and their related compounds on sodium currents were examined in internally perfused giant axons of crayfish under voltage clamp conditions. The compounds increased the steady-state sodium current and induced a residual current during step depolarization of the axonal membrane. They also induced a tail current upon step repolarization. Each of the ratios of the residual and tail sodium currents to the transient peak sodium current at each measurement increased with time after the start of the internal application of the compounds until a steady level was reached. The rate constants of the development of the two kinds of sodium currents, residual and tail, in terms of the ratios were estimated by use of first-order kinetics and had a linear relationship for this series of compounds. Variations in each of these rate constants among compounds were parabolically related with the hydrophobicity of the molecule, giving a common optimum log P ( P, the partition coefficient in the 1-octanol/water system) at about 4.6. The rate of development of the residual and tail currents is probably decided by the penetration rate of the compounds to the target site(s).