| 1375788 |
Bloomquist JR: Intrinsic lethality of chloride-channel-directed insecticides and convulsants in mammals. Toxicol Lett. 1992 May;60(3):289-98.
The intrinsic lethality of a series of chloride-channel-directed convulsants and insecticides was determined by intracerebral injection into mice. The toxicities of the cyclodiene insecticides and picrotoxinin were potentiated by intracerebral injection, when compared to their reported intraperitoneal LD50s. In contrast, the toxicities of lindane, abamectin, and the bicyclic convulsants TBPS and a TBOB analog were approximately the same by either route of administration. These results suggest that the brain is the primary target site for the cyclodienes and picrotoxinin, while the peripheral nervous system may be relatively more important in the toxic action of lindane, abamectin, and bicyclic convulsants such as TBPS. With the exception of picrotoxinin these compounds showed, overall, a good correlation between acute intracerebral toxicity and potency for inhibiting GABA-dependent chloride uptake. The evidence that multiple chloride-channel subtypes serve as targets for these compounds and the potential impact this had on the results of these studies are discussed. |
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