Phenylpyrazole insecticide photochemistry, metabolism, and GABAergic action: ethiprole compared with fipronil

J Agric Food Chem. 2003 Nov 19;51(24):7055-61. doi: 10.1021/jf030439l.

Abstract

Ethiprole differs from fipronil, the major phenylpyrazole insecticide, only in an ethylsulfinyl substituent replacing the trifluoromethylsulfinyl moiety. This study compares their photochemistry, metabolism, action at the gamma-aminobutyric acid (GABA) receptor, and insecticidal potency. On exposure to sunlight as a thin film, ethiprole undergoes oxidation (major), reduction, and desethylsulfinylation but not desulfinylation whereas the major photoreaction for fipronil is desulfinylation. Metabolic sulfone formation is more rapid with ethiprole than fipronil in human expressed CYP3A4 in vitro and mouse brain and liver in vivo. High biological activity is observed for the sulfide, sulfoxide, sulfone, and desulfinyl derivatives in both the ethiprole and the fipronil series in GABA receptor assays (human recombinant beta3 homomer and house fly head membranes) with [(3)H]EBOB and in topical toxicity to house flies with and without the P450-inhibiting synergist piperonyl butoxide. On an overall basis, the ethiprole series is very similar in potency to the fipronil series.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Houseflies
  • Humans
  • Insecticides* / chemistry
  • Insecticides* / metabolism
  • Insecticides* / pharmacology
  • Liver / metabolism
  • Male
  • Mice
  • Oxidation-Reduction
  • Photochemistry
  • Pyrazoles / chemistry*
  • Pyrazoles / metabolism*
  • Pyrazoles / pharmacology
  • Receptors, GABA / drug effects*
  • Receptors, GABA / metabolism
  • Recombinant Proteins
  • Sulfones / metabolism

Substances

  • Insecticides
  • Pyrazoles
  • Receptors, GABA
  • Recombinant Proteins
  • Sulfones
  • ethiprole
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • fipronil