title: Inhibition of monoamine oxidase A-form and semicarbazide-sensitive amine oxidase by selective and reversible monoamine oxidase-A inhibitors, amiflamine and FLA 788(+).
abstract: In vitro studies demonstrated that two selective monoamine oxidase (MAO)-A inhibitors, amiflamine and FLA 788(+), have been shown to inhibit semicarbazide-sensitive amine oxidase (SSAO) in rat testis and lung homogenates in a concentration-dependent way. The inhibition was not greatly influenced by pretreatment of the preparations with either clorgyline (10(-3) mol/l), l-deprenyl (10(-3) mol/l) or SKF 525A (10(-4) mol/l). The two compounds showed a time-dependent inhibition of SSAO, and for the initial phase of the inhibition, amiflamine is a competitive inhibitor with a Kislope of 135 mumol/l, but FLA 788(+) is a noncompetitive inhibitor with a Ki value of 180 mumol/l. After preincubation for 60 min at 37 degrees C, however, inhibition by amiflamine was found to be essentially irreversible whereas that produced by FLA 788(+) was still noncompetitive and reversible. These two compounds also reversibly and competitively inhibited rat testis MAO-A with FLA 788(+) being much more selective towards this MAO (Kislope = 0.26 mumol/l for FLA 788(+) and 7 mumol/l for amiflamine, respectively). The present results indicate that both MAO-A-selective inhibitors also inhibit SSAO in vitro, but their properties as SSAO inhibitors differ from those as MAO-A inhibitors.
mesh_terms: D000818:Animals; D001595:Benzylamine Oxidase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008995:Monoamine Oxidase; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000187:drug effects / Q000201:enzymology; D013997:Time Factors
chemical_list: D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; C034683:4-methylamino-alpha,2-dimethylphenethylamine; D001595:Benzylamine Oxidase; D008995:Monoamine Oxidase; C031466:amiflamine