Quantitative structure-activity studies of substituted benzyl chrysanthemates: 1. Correlations between symptomatic and neurophysiological activities against American cockroaches

Abstract

A number of substituted benzyl (1R)-trans-chrysanthemates and related compounds were synthesized. Their symptomatic activities in terms of levels which induce convulsions as well as cause death in American cockroaches were determined by injection with and without application of synergists as inhibitors of metabolism. The neuroexcitatory and neuroblocking activities were also determined in terms of minimum effective concentrations to induce repetitive train of impulses and conduction blockage, respectively, to central nerve cords excised from the cockroaches and immersed in Ringer's solution. Correlations between symptomatic and neurophysiological activities were analyzed quantitatively with the aid of molecular hydrophobicity parameter and regression analysis. Each symptomatic activity from which the effect of metabolism is eliminated was found to be analyzable by means of a linear combination of indices for two types of neurophysiological activity when the transport factor is separated by using the hydrophobicity parameter. A closer correlation was found between neuroblocking activity and the “convulsive” effect than between neuroexcitatory activity and the “convulsive” effect, whereas both neurophysiological effects operate together on the cockroaches resulting in paralysis and death.