MD 240928 and harmaline: opposite selectivity in antagonism of the inactivation of types A and B monoamine oxidase by pargyline in mice.
In mice treated 24 hrs earlier with pargyline (20 mg/kg i.p), both type A and type B monoamine oxidase (MAO-A and MAO-B) were partially inactivated in brain, heart and liver. The abilities of two short-acting, reversible inhibitors of MAO to antagonize that inactivation were compared. Pretreatment with MD 240928 at doses of 10, 20 or 30 mg/kg i.p. antagonized the inactivation of type B MAO but did not alter the inactivation of type A MAO in all three tissues. In contrast, pretreatment with harmaline at a dose of 10 mg/kg i.p. antagonized the inactivation of type A MAO but did not alter the inactivation of type B MAO. Antagonism of the pargyline-induced inactivation is interpreted as being due to the transient selective inhibition of MAO-A by harmaline and of MAO-B by MD 240928, preventing the mechanism-based inactivation of those enzymes by pargyline. The selective protection by harmaline is in agreement with earlier results with that compound in rats; the selective protection by MD 240928 is the first report of selective protection against MAO-B inactivation.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology; D006246:Harmaline / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology; D010080:Oxazoles / Q000494:pharmacology*; D023303:Oxazolidinones; D010293:Pargyline / Q000494:pharmacology*; D013997:Time Factors
D000470:Alkaloids; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D023303:Oxazolidinones; C037871:MD 780236; D010293:Pargyline; D006246:Harmaline; D008995:Monoamine Oxidase