Quantitative structure-activity studies of substituted benzyl chrysanthemates: 9. Calcium uptake inhibition in crayfish nerve cord and lobster axon homogenates in vitro by sunthetic pyrethroids

Twenty-five synthetic pyrethroids and related chemicals were assessed for their effects on the uptake of Ca²⁺ (as ⁴⁵Ca²⁺) by crude homogenates prepared from crayfish (Procambarus clarkii) nerve cords and 20 were assessed on the uptake by homogenates prepared from lobster (Panulirus japonicus) axons. A parabolic relationship was demonstrated between inhibition of Ca²⁺ uptake for this series of chemicals and lipophilicity (log P) in both species when tested at 5 μM. Optimal log P for maximal inhibition was located at about 6.6 and 84(±6)% inhibition was obtained with resmethrin. Compounds of higher or lower log P were either weaker inhibitors, not inhibitors or occasionally resulted in slightly increased levels of Ca²⁺ uptake. No direct correlations between the potential for the pyrethroids to inhibit Ca²⁺ uptake and the potential for these agents to increase the frequency of spontaneous discharges in crayfish nerve cords, to induce repetitive firing in American cockroaches, or the lethality to cockroaches or to any other neurophysiological or toxicity parameter could be established. It was concluded that although some synthetic pyrethroids are moderately potent inhibitors of Ca²⁺ uptake into nerve cord and axonic preparations (i.e., I₅₀ for trans-resmethrin equals 1 μM) this inhibition alone does not relate to the neurophysiological changes in isolated nerve preparations or to the toxicity of these agents in insects.