Neurotoxic effects of paraoxon and isofenphos on the ventral nerve cord of the American cockroach, Periplaneta americana

摘要

The phosphoramidates are a group of organophosphates whose mode of action is not as clear as other activated phosphates. To better understand the mode of action of phosphoramidates, the insecticidal activity and relative potency of paraoxon and the aryl phosphoramidate isofenphos (0-ethyl 0-(2-isopropoxycarbonyl)- phenyl isopropylphosphoramidothioate) and its metabolites, iso- fenphos oxon, des-N-isopropyl isofenphos (DNI) and des-N-iso- propyl isofenphos oxon (DNIO) were examined using the American cockroach, Periplaneta americana. Each chemical was dissolved in saline and applied to the ventral nerve cord (VNC) of a dissected cockroach. The electrical response of the normally quiescent giant interneurons (GIs) to each chemical was recorded extracellularly from the VNC. Although all compounds tested evoked repeated, high-frequency bursting activity in GIs, the GIs appeared most sensitive to the oxons, especially DNIO. The mean time from application (10 ppm) to the VNC until the induction of GI bursting was 2.3, 10.8, 32.5, and 40 min for paraoxon, DNIO, isofenphos oxon, DNI, and isofenphos. The correlation between the time to GI bursting and cholinesterase inhibition by DNIO suggests that one of the modes of action of iso- fenphos is cholinesterase inhibition through its metabolite DNIO. Incubation of DNIO with VNC cholinesterase showed that DNIO is a good cholinesterase inhibitor, but isfenphos and the other metabolites showed weak inhibition at concentrations 400 Hz) of small spikes (amplitude = 2-8 mV) that often triggered large overshooting spikes (up to 90 mV). Recordings from multiple sites indicated these spikes originated within A6. Also, no waves or bursting were seen following application of paraoxon to GIs isolated by ligation from their cell bodies and cercal sensory inputs.