Inhibition of semicarbazide-sensitive amine oxidase by monoamine oxidase B inhibitors from the oxazolidinone series.
The purpose of the present work was to study the semicarbazide-sensitive amine oxidase (SSAO) inhibitory properties of MD 240931 and MD 240928 (the two enantiomers of MD 780236) as well as those of the corresponding primary amines, MD220662 and MD220661, in rat heart and aorta. MD240928 and MD240931 are rather weak SSAO inhibitors, MD 240931 being more potent than MD 240928. Of the four compounds studied, the most potent inhibitor of SSAO is MD 220662, its IC50 value ranging from 2.10(-6) to 6.10(-6)M. The SSAO inhibitory potency of this compound does not change significantly with the time of preincubation in both the absence and presence of clorgyline (10(-4)M). MD 220661 is also an inhibitor of SSAO; however, its SSAO inhibitory potency, which without preincubation is comparable to that of MD 220662, does decrease with the time of preincubation to the same extent in both the absence and presence of clorgyline (10(-4)M). These results suggest that MD 220661 is not only an inhibitor of SSAO, but is also a substrate of the enzyme.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology; D010080:Oxazoles / Q000494:pharmacology*; D023303:Oxazolidinones; D051381:Rats; D011919:Rats, Inbred Strains; D012663:Semicarbazides / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D023303:Oxazolidinones; D012663:Semicarbazides; C043985:MD 220661; C037871:MD 780236; D003000:Clonidine