Monoamine oxidase-B inhibition: a comparison of in vivo and ex vivo measures of reversible effects.

A behavioural test involving potentiation of the effects of an acute injection of beta-phenylethylamine (10 mg kg-1 i.p.) was used to assess the time-course of type-B MAO inhibition after administration of (--)deprenyl (5 mg kg-1 i.p.) and of MD 240928 (20 mg kg-1 i.p.) respectively. Potentiation of the effects of beta-phenylethylamine was observed 1 h after injection of (-)deprenyl or MD 240928. This effect was still evident 120 h after administration of (-)deprenyl but not 24 h after administration of MD 240928. Comparisons of ex vivo estimates of MAO activity yielded a corresponding time-course for the recovery of this enzyme. The extent of MAO inhibition required for potentiation of the effects of beta-phenylethylamine was inferred from a comparison of the behavioural test results and the ex vivo MAO activity observed after (-)deprenyl administration. These comparisons indicate a significant underestimation of MD 240928-induced MAO inhibition using ex vivo measures. This underestimation is interpreted as evidence for dilution effects in the ex vivo assay of MAO inhibition. The potentiation of effects of beta-phenylethylamine under the present conditions is proposed as a useful and simple test for effects of reversible type-B MAO inhibitors.