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Science 30 September 1983:
Vol. 221. no. 4618, pp. 1399 - 1401
DOI: 10.1126/science.6310756
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Articles

Science, Vol 221, Issue 4618, 1399-1401
Copyright © 1983 by American Association for the Advancement of Science

articles

Stereospecific action of pyrethroid insecticides on the gamma-aminobutyric acid receptor-ionophore complex

LJ Lawrence and JE Casida

The potent alpha-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 gamma-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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Developmental Neurotoxicity of Pyrethroid Insecticides in Zebrafish Embryos.
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Relative Potencies for Acute Effects of Pyrethroids on Motor Function in Rats.
M. J. Wolansky, C. Gennings, and K. M. Crofton (2006)
Toxicol. Sci. 89, 271-277
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5-HT loss in rat brain by type II pyrethroid insecticides.
M. R Martinez-Larranaga, A. Anadon, M. A Martinez, M. Martinez, V. J Castellano, and M. J Diaz (2003)
Toxicology and Industrial Health 19, 147-155
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Repression of Activity-Dependent c-fos and Brain-Derived Neurotrophic Factor mRNA Expression by Pyrethroid Insecticides Accompanying a Decrease in Ca2+ Influx into Neurons.
L. Imamura, H. Hasegawa, K. Kurashina, A. Hamanishi, A. Tabuchi, and M. Tsuda (2000)
J. Pharmacol. Exp. Ther. 295, 1175-1182
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The Pyrethroids Permethrin and Cyhalothrin are Potent Inhibitors of the Mitochondrial Complex I.
B. Gassner, A. Wüthrich, G. Scholtysik, and M. Solioz (1997)
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