A STUDY OF THE BIOLOGICAL PHARMACOLOGY OF IFO, A NEW SELECTIVE AND REVERSIBLE MONOAMINE OXIDASE-B INHIBITOR

propoxy]phenyl]-5-trifluoromethyl-1,2,4-oxadiazole (IFO), designed to be a novel selective inhibitor of monoamine oxidase (MAO), showed high ly selective inhibition for type-B (MAO-B); its IC50 was approximately > 200 mu M and 30 nM for type-A (MAO-A) and MAO-B, respectively, in t he standard assay using mitochondrial preparations from rat brain or l iver. The in vitro MAO-B inhibition by IFO was time-independent, non-c ompetitive and tight-binding; and furthermore, in the presence of sodi um cholate its inhibition was not tight-binding and was reversible. Or al administration of IFO (0.5 - 100 mg/kg) produced a dose-dependent M AO-B inhibition in mouse brain; its ED(50) (p.o., 1 hr) was 1.6 mg/kg, while L-deprenyl inhibited the enzyme with the ED(50) of approximatel y 8.0 mg/kg. The ED(50) for MAO-A was > 100 mg/kg for either IFO and L -deprenyl. The MAO inhibitive effect of IFO in mouse liver was the sam e as that in the brain, but that of L-deprenyl in mouse liver was diff erent from that in the brain as shown by the ED(50) values of 35 mg/kg and 0.6 mg/kg for MAO-A and MAO-B, respectively. In mice, IFO increas ed the striatal concentrations of 2-phenylethylamine (2-PEA) and showe d almost the same protective efficacy as L-deprenyl against the lethal ity and striatal dopamine (DA) depletion induced by 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP). These results indicate that IFO app ears to be a potent inhibitor of MAO-B in mouse brain.