GABAergic Neurotransmission and Toxicity 1: Organochlorines

Abstract

In the 1950s, the introduction of organochlorine insecticides containing active ingredients such as lindane, dieldrin, endrin, chlordane, heptachlor, endosulfan and toxaphene was extremely effective in combating a wide variety of crop and livestock pests. In the 1980s, the inhibitory molecular action causing convulsions and neurotoxicity was identified as binding to the pre-synaptic γ-aminobutyric acid-binding receptor A (GABAA)-regulated chloride channel, near to the picrotoxinin-binding site, antagonising membrane hyperpolarisation and inward chloride current. However, it became evident that the properties that made them excellent insecticides might also make them toxic to humans and non-target animal species. Accidental, occupational and suicidal convulsions occurred in humans, and there were marked effects on wildlife, especially in birds, due to accumulation up the food chain. Differential metabolism was an important factor determining the differences between individual insecticides. After a few decades of use, these pesticides were phased out and banned. The now-established multiple aspects of their toxicity in vivo or in vitro continue to be of concern regarding their possible adverse effects on human health through environmental exposure.