Selective inhibition of monoamine oxidase type B by MDL 72145 increases the central effects of L‐DOPA without modifying its cardiovascular effects

Abstract

The potential of a new, potent, irreversible and selective inhibitor of monoamine oxidase type B, (E)‐2‐(3,4‐dimethoxyphenyl)‐3‐fluorallyamine (MDL 72145), to augment the effects of L‐DOPA in an animal model which reproduces the biochemical defect of Parkinson's disease has been evaluated. In rats bearing unilateral 6‐hydroxydopamine lesions of the nigro‐striatal dopamine pathways, both MDL 72145 and clorgyline, a selective inhibitor of MAO A, augmented the contralateral turning response to L‐DOPA combined with carbidopa. The potential of inhibitors of MAO to interact adversely in the periphery with L‐DOPA was investigated in the pithed rat; L‐DOPA was given either intravenously or intraduodenally. Clorgyline consistently potentiated L‐DOPA when given 18 h before testing. Neither MDL 72145 nor the selective inhibitor of MAO B, L‐deprenyl, augmented the cardiovascular effects of intraduodenally administered L‐DOPA. The data provide no reason to suppose that MDL 72145 would be very different in clinical use from L‐deprenyl which is both effective and well‐tolerated as an adjunct to the L‐DOPA‐based therapy of Parkinson's disease.