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Stereospecific Action of Pyrethroid Insecticides on the γ-Aminobutyric Acid Receptor-Ionophore Complex
Abstract
The potent α-cyano-3-phenoxybenzyl pyrethroids, including cypermethrin, deltamethrin, and fenvalerate, act stereospecifically to inhibit binding to rat brain synaptic membranes of sulfur-35-labeled t -butylbicyclophosphorothionate, a new radioligand for the picrotoxinin binding site. Scatchard analysis indicates that picrotoxinin inhibition of t -butylbicyclophosphorothionate binding is competitive whereas cypermethrin inhibition possibly involves a closely associated site in the γ-aminobutyric acid receptor-ionophore complex. Studies with 37 pyrethroids reveal an absolute correlation, that is, no false positives or negatives, between mouse intracerebral toxicity and in vitro inhibition: all toxic cyano compounds but none of their nontoxic stereoisomers are inhibitors; cis isomers are more potent than trans isomers as both toxicants and inhibitors; and noncyano pyrethroids are much less potent or are inactive.
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Citations
Cited by
Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment
Soderlund, D. M., Clark, J. M., Sheets, L. P., Mullin, L. S., Piccirillo, V. J., Sargent, D., Stevens, J. T., & Weiner, M. L. (2002) · Toxicology · doi:10.1016/s0300-483x(01)00569-8 · Cited by 1,015
GABA receptor mechanisms in the central nervous system
Sivilotti, L., & Nistri, A. (1991) · Progress in Neurobiology · doi:10.1016/0301-0082(91)90036-z · Cited by 554
Maternal lifestyle and environmental risk factors for autism spectrum disorders
Lyall, K., Schmidt, R. J., & Hertz-Picciotto, I. (2014) · International Journal of Epidemiology · doi:10.1093/ije/dyt282 · Cited by 427
Comparative Toxicology of the Pyrethroid Insecticides
Bradbury, S. P., & Coats, J. R. (1989) · Reviews of Environmental Contamination and Toxicology · doi:10.1007/978-1-4613-8850-0_4 · Cited by 354
Fish acute toxicity syndromes and their use in the QSAR approach to hazard assessment
McKim, J. M., Bradbury, S. P., & Niemi, G. J. (1987) · Environmental Health Perspectives · doi:10.1289/ehp.8771171 · Cited by 210
Metadata
- Authors
- Lawrence, L. J., & Casida, J. E.
- Venue
- Science
- Published
- 1983-09-30
- Volume
- 221
- Issue
- 4618
- Pages
- 1399-1401
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1980613202
- Cited by
- 233
- References
- 0
- FWCI
- 27.09
- Type
- journal article
- Language
- en
- Open access
- closed
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- Lawrence, L. J., & Casida, J. E. (1983). Stereospecific Action of Pyrethroid Insecticides on the γ-Aminobutyric Acid Receptor-Ionophore Complex. Science. https://doi.org/10.1126/science.6310756
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