Studies on the metabolism, mode of action, and development of insecticides acting on the GABA receptor

Journal of Pesticide Science
Keiji Tanaka

Abstract

γ-BHC and dieldrin are legacy insecticides that were extensively used after the second World War. When they were banned, their modes of action and metabolism were not known. This article aims at providing a picture of the metabolism of γ-BHC and the modes of action of γ -BHC and dieldrin. γ-BHC is metabolized via two independent metabolic pathways. One is a glutathione conjugation pathway resulting in the formation of dichlorophenyl mercapturic acid and the other is an oxidative metabolism catalyzed by microsomes to mainly 2,4,6-trichlorophenol (TCP) and (36/45)-1,2,3,4,5,6-hexachlorocyclohex-1-ene (HCCHE). Other metabolites of this pathway are 2,4,5-TCP, 2,3,4,6-tetrachlorophenol (TeCP), (36/45)- and (346/5)-1,3,4,5,6-pentachlorocyclohex-1-enes (PCCHE). Nowadays, γ-BHC and dieldrin are very important reagents which are used to study the GABA receptor in insects and mammals. They were found to be noncompetitive GABA antagonists blocking the chloride ion selective pores in the GABA-gated chloride channels and leading to inhibition of chloride ion conductance. [3H]EBOB binding data showed that γ-BHC, its analogs, dieldrin, and other cyclodiene insecticides interact with the same site on GABA receptor as picrotoxinin. Only γ-BHC, ...Continue Reading

References

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Citations

Mar 8, 2020·Toxicology Letters·Athina-Maria AloizouEfthimios Dardiotis
Apr 4, 2020·Journal of Agricultural and Food Chemistry·Genyan LiuYoshihisa Ozoe

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