propoxy]phenyl]-5-trifluoromethyl-1,2,4-oxadiazole (IFO), design ed to be a novel selective inhibitor of monoamine oxidase (MAO), showed highly selective inhibition for type-B (MAO-B); its IC50 was approximately > 200 pM and 30 nM for type-A (MAO-A) and MAO-B, respectively, in the standard assay using mitochondrial preparations from rat brain or liver. The in vitro MAO-B inhibition by IFO was time-independent, non-competitive and tight-binding; and furthermore, in the presence of sodium cholate its inhibition was not tight-binding and was reversible. Oral administration of IFO (0.5 -100 mg/kg) produced a dose-dependent MAO-B inhibition in mouse brain; its ED50 (p.o., 1 hr) was 1.6 mg/kg, while L-deprenyl inhibited the enzyme with the ED50 of approximately 8.0 mg/kg. The ED50 for MAO-A was > 100 mg/kg for either IFO and L-deprenyl. The MAO inhibitive effect of IFO in mouse liver was the same as that in the brain, but that of L-deprenyl in mouse liver was different from that in the brain as shown by the ED50 values of 35 mg/kg and 0.6 mg/kg for MAO-A and MAO-B, respectively. In mice, IFO increased the striatal concentrations of 2-phenylethylamine (2-PEA) and showed almost the same protective efficacy as L-deprenyl against the lethality and striatal dopamine (DA) depletion induced by 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). These results indicate that IFO appears to be a potent inhibitor of MAO-B in mouse brain.

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Abstract-A newly synthesized compound, [[3-(1 H-tetrazol-5-yl)-phenyl] amino]oxoacetic acid n-butyl ester (MTB) has been demonstrated to be an orally active antiallergic agent. This compound inhibited the 48-hr passive cutaneous anaphylaxis (48-hr PCA) induced by IgE in rats. In guinea pigs, MTB also inhibited the 8-day passive cutaneous anaphylaxis (8-day PCA) and the 8-day passive systemic anaphylaxis induced by IgE. The compound partially inhibited the IgG-mediated 3-hr PCA in rats and guinea pigs, but failed to have any effect on the rabbit IgG-mediated 3-hr PCA in these animals. In the rat, MTB was not an antagonist of histamine or serotonin. The antiallergic effect of MTB was not mediated via any adrenergic mecha nisms. MTB significantly inhibited histamine release from rat peritoneal cells induced by rat IgE in vitro.

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