Neurobehavioral toxicology of pyrethroid insecticides
Pyrethroid insecticides are classified as either Type I or Type II based upon in vivo toxic signs, and neurophysiological and biochemical data. Both axonal sodium channels and the ..gamma..-aminobutyric acid (GABA) receptor complex have been proposed as the major site of action of the Type II pyrethroids. This investigation characterized the behavior and biochemical effects of low dosages of pyrethroids in rats. Type I and II pyrethroids were tested for effects on figure-eight maze activity and the acoustic startle response (ASR). All compounds decreased figure-eight maze activity. Interactions of Type I and II pyrethroids with the three major binding sites on the GABA complex were determined in vivo. Radioligand binding experiments assessed in vitro interactions of pyrethroids with the three major GABA-complex binding sites. None of the pyrethroids competed for (/sup 3/H)-muscimol or (/sup 3/H)-flunitrazepam binding. Only Type II pyrethroids inhibited binding of (/sup 35/S)-t-butylbicyclophosphorothionate (TBPS) in cortical synaptosome preparations with K/sub i/ values of 5 to 10 ..mu..M. The (/sup 35/S)-TBPS data implicate the TBPS/picrotoxinin binding site in the mechanism of Type II pyrethroid toxicity. The results of these experiments support the classification of pyrethroids into two classes, and demonstrate the utility of the figure-eight maze and the ASR in studies to elucidate neurotoxic mechanisms. The interaction of the Type II pyrethroids is probably restricted to the TBPS/picrotoxinin binding domain on the GABA complex as shown by both the in vivo and in vitro studies.
- Research Organization:
- North Carolina Univ., Chapel Hill (USA)
- OSTI ID:
- 5598243
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
Similar Records
Binding interactions of convulsant and anticonvulsant gamma-butyrolactones and gamma-thiobutyrolactones with the picrotoxin receptor
Structure-activity correlations for interactions of bicyclophosphorus esters and some polychlorocycloalkane and pyrethroid insecticides with the brain-specific t-butylbicyclophosphorothionate receptor
Related Subjects
INSECTICIDES
BIOLOGICAL EFFECTS
RADIORECEPTOR ASSAY
AMINOBUTYRIC ACID
BEHAVIOR
BIOCHEMISTRY
HETEROCYCLIC COMPOUNDS
RATS
SULFUR 35
TRITIUM COMPOUNDS
AMINO ACIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DRUGS
EVEN-ODD NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
NEUROREGULATORS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PESTICIDES
RADIOISOTOPES
RODENTS
SULFUR ISOTOPES
TRACER TECHNIQUES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics