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• W2080351738 abstract "This study assessed the toxicity and mode of action of a new experimental insecticide, LY219048 in insects and mammals. LY219048 produced rapid convulsions in mice and had LD50 values of 0.7 mg kg−1 and 4 mg kg−1 after intracerebral and intraperitoneal injection, respectively. In initial screens against insects, LY219048 showed low activity against the German cockroach (Blatella germanica L.). Lethality from dietary exposure required one to two weeks, even at concentrations as high as 10000 mg kg−1 (LC50 = 485 mg kg−1). In contrast, it had an LC50 value of 8.3 mg kg−1 against insecticide-susceptible Drosophila melanogaster (Meig.) when synergized with piperonyl butoxide. Significant resistance to LY219048 (> 12-fold) was detected in a cyclodiene-resistant strain of D. melanogaster possessing an altered target site resistance mechanism. This finding suggested that LY219048 blocked the 4-aminobutyric acid (GABA)-gated chloride channel in a manner similar to that of the cyclodienes. In physiological studies in larval D. melanogaster central neurons, LY219048 antagonized the reduction of firing caused by 1 mM GABA. Dose-response experiments showed that the ED50 for blocking inhibition under these conditions was c. 1 μ. Studies of 36CI uptake into bovine brain synaptosomes found that LY219048 was a potent antagonist. At 10 μ it completely blocked chloride flux stimulated by 50 μM GABA. LY219048 competitively displaced [3H]TBOB binding from bovine brain membranes, with an IC50 of 42 nM, which was comparable to values determined for TBPS (35 nM) and picrotoxinin (267 nM). There was little or no displacement (<25%) of [3H]flunitrazepam or [3H]muscimol binding by 10 μM LY219048. Taken together, these results provide strong evidence that this new chemical class of insecticide manifests its acute toxicity by blocking the GABA-gated chloride channel." @default.
• W2080351738 created "2016-06-24" @default.
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• W2080351738 date "1993-01-01" @default.
• W2080351738 modified "2023-09-27" @default.
• W2080351738 title "Spirosultam LY219048: A new chemical class of insecticide acting upon the GABA receptor/chloride ionophore complex" @default.
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• W2080351738 doi "https://doi.org/10.1002/ps.2780390304" @default.
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