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

Abstract

A behavioural test involving potentiation of the effects of an acute injection of β-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 β-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 β-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 fordilution effects in the ex vivo assay of MAO inhibition. The potentiation of effects of β-phenylethylamine under the present conditions is proposed as a useful and simple test for effects of reversible type-B MAO inhibitors.