Related Experiment Videos
Intrinsic lethality of chloride-channel-directed insecticides and convulsants in mammals
1Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg 24061.
Abstract:
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.
Insights
Insecticides targeting chloride channels show varied toxicity based on administration route. Brain is key for cyclodienes and picrotoxinin, while peripheral nerves matter more for lindane and abamectin.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Chloride channels are crucial for neuronal function.
- Convulsants and insecticides often target these channels.
- Understanding target sites is key to assessing toxicity.
Purpose of the Study:
- To compare the intrinsic lethality of chloride-channel-directed agents via intracerebral vs. intraperitoneal injection in mice.
- To elucidate the primary target sites (central vs. peripheral nervous system) for these compounds.
- To correlate acute toxicity with the inhibition of GABA-dependent chloride uptake.
Main Methods:
- Determination of intrinsic lethality through intracerebral injection in mice.
- Comparison of intracerebral LD50 values with reported intraperitoneal LD50s.
- Assessment of compound potency in inhibiting GABA-dependent chloride uptake.
Main Results:
- Cyclodiene insecticides and picrotoxinin showed potentiated toxicity via intracerebral injection.
- Lindane, abamectin, TBPS, and TBOB analog exhibited similar toxicity regardless of administration route.
- A strong correlation was observed between intracerebral toxicity and inhibition of GABA-dependent chloride uptake, except for picrotoxinin.
Conclusions:
- The brain is the primary target for cyclodienes and picrotoxinin.
- The peripheral nervous system may play a more significant role in the toxicity of lindane, abamectin, and bicyclic convulsants.
- Multiple chloride channel subtypes likely serve as targets, influencing observed toxicological profiles.