Specific inhibition of polyamine oxidase in vivo is a method for the elucidation of its physiological role.
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.
D000818:Animals; D001921:Brain / Q000201:enzymology; D002251:Carbon Tetrachloride / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D011700:Putrescine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013095:Spermidine / Q000031:analogs & derivatives / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives / Q000378:metabolism; D000097667:Polyamine Oxidase
D002251:Carbon Tetrachloride; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011700:Putrescine; D013095:Spermidine; D013096:Spermine; D000097667:Polyamine Oxidase; C017988:N(1)-acetylspermidine; C044445:MDL 72527; C029452:N'-acetylspermine; C044444:N-methyl-N-(2,3-butadienyl)-1,4-butanediamine; C044443:N-methyl-N-(2-propenyl)-1,4-butanediamine