title: Stereospecific action of pyrethroid insecticides on the gamma-aminobutyric acid receptor-ionophore complex.
abstract: 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.
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007306:Insecticides / Q000494:pharmacology*; D007476:Ionophores / Q000037:antagonists & inhibitors; D010852:Picrotoxin / Q000378:metabolism; D011485:Protein Binding; D011722:Pyrethrins / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013570:Synaptic Membranes / Q000378:metabolism
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007306:Insecticides; D007476:Ionophores; D010852:Picrotoxin; D011722:Pyrethrins; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; C037476:tert-butylbicyclophosphorothionate