Evidence for similarities between cyclodiene type insecticides and picrotoxinin in their action mechanisms.
Evidence has been obtained to indicate that cyclodiene-type insecticides, e.g., heptachlor epoxide and gamma-BHC, mimic the action of picrotoxinin. These insecticides inhibit the GABA (gamma-aminobutyric acid)-stimulated chloride uptake in the coxal muscle of the American cockroach, and directly compete against [3H]a-dihydropicrotoxinin for binding in the rat brain synaptosomes. Moreover, several cyclodiene-resistant insect strains are also resistant to picrotoxinin. This cross-resistance is specific to picrotoxinin and does not extend to other neuroexcitants. These insecticides, like picrotoxinin, cause central nerve excitation by stimulating transmitter release. Similarity in molecular structures also has been pointed out. These results indicate that some of the nerve excitation symptoms that insecticides cause are likely due to their interaction with picrotoxinin receptor.
D000818:Animals; D001667:Binding, Competitive; D002712:Chlorides / Q000378:metabolism*; D003058:Cockroaches / Q000378:metabolism*; D004351:Drug Resistance; D006533:Heptachlor / Q000031:analogs & derivatives*; D006534:Heptachlor Epoxide / Q000494:pharmacology*; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010526:Periplaneta / Q000378:metabolism*; D010852:Picrotoxin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011963:Receptors, GABA-A; D054830:Sesterterpenes; D013574:Synaptosomes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002712:Chlorides; D006533:Heptachlor; D006534:Heptachlor Epoxide; D001556:Hexachlorocyclohexane; D010852:Picrotoxin; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D054830:Sesterterpenes; D005680:gamma-Aminobutyric Acid; C031012:dihydropicrotoxinin receptor; C017230:dihydropicrotoxinin; C022961:picrotoxinin