γ-Lindane

γ-Lindane is an organochloro insecticide that is an antagonist of GABA_A receptors.¹ It inhibits GABA-stimulated chloride uptake by membrane vesicles isolated from rat cerebral cortex (IC₅₀ = 68 μM). It binds selectively to insect GABA_A receptors over mammalian GABA_A receptors in membrane preparations (IC₅₀s = 1, 12, 505, 833, and 150-1, 675 nM for fruit fly, house fly, human, mouse, and rat, respectively).^2,3 It binds to a human recombinant β₃ homooligomer with similar selectivity as α₁β₃γ₂-containing receptors, indicating that the binding site for γ-lindane on GABA_A receptors is located on the β₃ subunit (IC₅₀s = 0.90, 21, and 306 nM for β₃, α₁β₃γ₂, and the native receptor, respectively).⁴ γ-Lindane blocks GABA- and glutamate-induced current responses in American cockroach neurons (IC₅₀s = 1.74 and 148 nM, respectively).⁵ It is toxic to mice and adult house flies (LD₅₀s = 40 and 5.5 mg/kg, respectively) and also kills head lice in vitro and inhibits hatching.^4,6

1.Obata, T., Yamamura, H.I., Malatynska, E., et al.Modulation of ?-aminobutyric acid-stimulated chloride influx by bicycloorthocarboxylates, bicyclophosphorus esters, polychlorocycloalkanes and other cage convulsantsJ. Pharmacol. Exp. Ther.244(3)802-806(1988) 2.Hainzl, D., Cole, L.M., and Casida, J.E.Mechanisms for selective toxicity of fipronil insecticide and its sulfone metabolite and desulfinyl photoproductChem. Res. Toxicol.11(12)1529-1535(1998) 3.Llorens, J., SuÑol, C., Tussel, J.M., et al.Lindane inhibition of [35S]TBPS binding to the GABAA receptor in rat brainNeurotoxicol. Teratol.12(6)607-610(1990) 4.Ratra, G.S., Kamita, S.G., and Casida, J.E.Role of human GABAA receptor β3 subunit in insecticide toxicityToxicol. Appl. Pharmacol.172(3)233-240(2001) 5.Ihara, M., Ishida, C., Okuda, H., et al.Differential blocking actions of 4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB) and ?-hexachlorocyclohexane (?-HCH) on ?-aminobutyric acid- and glutamate-induced responses of American cockroach neuronsInvert. Neurosci.5(3-4)157-164(2005) 6.Meinking, T.L., Taplin, D., Kalter, D.C., et al.Comparative efficacy of treatments for pediculosis capitis infestationsArch. Dermatol.122(3)267-271(1986)