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Glutamate receptor inhibitors as potential insecticides.
Eldefrawi, M E; Anis, N A; Eldefrawi, A T.
Afiliación
  • Eldefrawi ME; Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore 21201.
Arch Insect Biochem Physiol ; 22(1-2): 25-39, 1993.
Article en En | MEDLINE | ID: mdl-8431599
Philanthotoxin (PhTX) is a neurotoxic constituent of the paralytic venom of the digger wasp, Philanthus triangulum. PhTX inhibits glutamate receptors of insect muscles mostly as a channel blocker, thereby producing muscle paralysis. Since glutamate receptor blockers may be of value as selective insect control agents, numerous derivatives of PhTX were synthesized and tested for their potencies as inhibitors of insect skeletal muscle glutamate receptors. Structure-activity relationship studies revealed that shortening the polyamine chain length reduced potency, and quaternarization of the nitrogen destroyed it. The potency was increased by a bulky anchoring group with moderate hydrophobicity at the end of the polyamine chain. The conversion of the tryosyl moiety to 3,5-diiodo-tyrosyl also increased potency and so did lengthening the butyryl chain from 4 to 10 carbons. Not only did PhTXs inhibit different subtypes of glutamate receptors, including the mammalian N-methyl-D-aspartate receptor, but also nicotinic receptors of insects and vertebrates. Because of this low selectively, and the hydrophilicity of the derivatives tested, which interferes with their penetration to the target receptor, these compounds cannot be used as insecticides. Nevertheless, the insect skeletal muscle glutamate receptor is a viable target for selective insecticides and major changes in PhTX structure may possibly produce derivatives that can be potential insecticides.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Poliaminas / Venenos de Avispas / Antagonistas de Aminoácidos Excitadores / Insecticidas Límite: Animals Idioma: En Revista: Arch Insect Biochem Physiol Asunto de la revista: BIOLOGIA / BIOQUIMICA Año: 1993 Tipo del documento: Article Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Poliaminas / Venenos de Avispas / Antagonistas de Aminoácidos Excitadores / Insecticidas Límite: Animals Idioma: En Revista: Arch Insect Biochem Physiol Asunto de la revista: BIOLOGIA / BIOQUIMICA Año: 1993 Tipo del documento: Article Pais de publicación: Estados Unidos