Excitatory Amino Acid Antagonists Alleviate Convulsive and Toxic Properties of Lindane in Mice

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Pesticides acting at GABAA receptors may induce convulsions in man and animals, but the mechanisms responsible for their convulsant activity are not fully explained. The following excitatory amino acid antagonists were studied for their protective action in mice intoxicated with chlorinated hydrocarbon insecticide lindane (γ-hexachlorocyclohexane): the competitive NMDA antagonist: 3-(2-carboxypiperazine-4-yl)propenyl-1-phosphonic acid (D-CPPene, 20 mg/kg), the non-competitive NMDA antagonist: dizocilpine (MK-801, 0.4 mg/kg), the glycine site antagonist of NMDA receptor: 2-phenyl-1,3-propane-diol dicarbamate (felbamate, 400 mg/kg) and the competitive AMPA antagonist: 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline(NBQX, 100 mg/kg). Systemic administration of an antagonist prior to lindane resulted in a strong anticonvulsant effect. D-CPPene, MK-801 and NBQX produced a marked increase of CD50 values of lindane for clonic convulsions. All the antagonists protected animals against tonic convulsions. Toxicity of lindane was potently reduced, as assessed 2, 24 and 120 hr after administration of the pesticide. Our results demonstrate that excitatory amino acid antagonists reduce convulsant properties and toxicity of lindane, suggesting that excitatory amino acid neurotransmission may be involved in its central action.

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