Specific inhibition of polyamine oxidase in vivo is a method for the elucidation of its physiological role

Biochim Biophys Acta. 1985 Jan 28;838(1):69-76. doi: 10.1016/0304-4165(85)90251-x.

Abstract

N1-Methyl-N2-(2,3-butadienyl)-1,4-butanediamine (MDL 72521) and N1,N2-bis(2,3-butadienyl)-1,4-butanediamine (MDL 72527) are specific, potent, enzyme-activated, irreversible inhibitors of polyamine oxidase in vitro. These compounds are also capable of completely inhibiting polyamine oxidase in mouse tissues at intraperitoneal doses greater than 20 mg/kg. Enzyme activity reappears in the various organs within 2-3 days to 50% of the control values. Irreversible inhibition of polyamine oxidase in mice led to decreased putrescine (30-40%) and spermidine (10-20%) levels in liver and some other organs. At the same time N1-acetylspermidine and, to a lesser extent, N1-acetylspermine were accumulating at rates which are assumed to be related to the rates of polyamine degradation. Even after treatment with polyamine oxidase inhibitors over a period of 6 weeks at doses which produced complete inhibition of polyamine oxidase in all organs, including the brain, neither toxic effects nor changes in body weight or behaviour were observed.

MeSH terms

  • Animals
  • Brain / enzymology
  • Carbon Tetrachloride / pharmacology
  • Dose-Response Relationship, Drug
  • Kidney / enzymology
  • Kinetics
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Mice
  • Oxidoreductases Acting on CH-NH Group Donors / antagonists & inhibitors*
  • Putrescine / analogs & derivatives*
  • Putrescine / metabolism
  • Putrescine / pharmacology
  • Spermidine / analogs & derivatives
  • Spermidine / metabolism
  • Spermine / analogs & derivatives
  • Spermine / metabolism

Substances

  • N(1)-acetylspermidine
  • MDL 72527
  • N'-acetylspermine
  • Spermine
  • N-methyl-N-(2,3-butadienyl)-1,4-butanediamine
  • N-methyl-N-(2-propenyl)-1,4-butanediamine
  • Carbon Tetrachloride
  • Oxidoreductases Acting on CH-NH Group Donors
  • polyamine oxidase
  • Spermidine
  • Putrescine