Abstract
γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter. The GABAa receptor is a primary target for cyclodiene insecticides and a secondary target for several other insecticides. The GABAa receptor has a high affinity (Kd in nM) for cyclodienes and binds them at the site that binds the convulsant t-butylbicyclophosphorothionate (TBPS). There is an excellent correlation between the toxicities of cyclodienes and their potencies in inhibiting receptor binding and function in mammalian brain and insect neurons. Of four hexachiorocyclohexane (BHC) isomers, only the insecticide γ-isomer inhibits the GABAa receptor. Other insecticides that inhibit this receptor are the pyrethroids, with type II more potent than type I, and a few organophosphate anticholinesterases (e.g. leptophos and EPN) with IC50 values above 1 μM. Voltage-dependent chloride channels are also targets for insecticides, possibly primary targets for avermectins. Also γ-BHC, is a potent inhibitor of a voltage-dependent chloride channel binding, even more so than of the GABAa receptor. However, the GABAa receptor binding site is much more stereospecific than that of the chloride channel.
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© 1989 Plenum Press, New York
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Eldefrawi, M.E., Eldefrawi, A.T. (1989). Insecticide Actions on Gaba Receptors and Voltage-Dependent Chloride Channels. In: Narahashi, T., Chambers, J.E. (eds) Insecticide Action. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1324-3_1
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