Novel substrates and products of amine oxidase-catalysed reactions.

Introduction Mitochondria1 monoamine oxidase (MAO; EC 1.4.3.4) catalyses the oxidative deamination of a variety of primary, secondary and tertiary amines. Until very recently most of the attention concerning MA0 activity was focused on the reaction of this enzyme to deaminate neurotransmitter substances, including adrenaline, noradrenaline, serotonin and dopamine. The ability of MA0 to regulate the intraneuronal concentration of aminergic neurotransmitters and tissue concentrations of other sympathomimetic amines, such as tyramine, phenylethylamine and tryptamine, conferred a detoxifying role on this enzyme (see [l , 2J for reviews). However, more recent studies and developments in the reaction kinetics of MA0 indicate that this enzyme may have other functional roles and, indeed, may be involved in converting rather inert tertiary amines, such as the Parkinson-inducing dopaminergic neurotoxin MPTP (N-methyl-4phenyl-l,2,3,6-tetrahydropyridine) to the neuroactive metabolite MPP+ (N-methyl-4-phenyl-l,2dihydropyridinium ion) [3]. Thus, MA0 has also been assigned a role in the pathogenesis of Parkinson’s disease, resulting from its ability to convert (oxidize) environmental MPTP-like neurotoxins to reactive metabolites. Although MPTP is a synthetic amine, such suggestions cannot be ignored, even though no such Parkinson disease-inducing environmental neurotoxin has so far been identified in the environment or the human brain. In this paper we wish to describe a recentlydiscovered novel property of MA0 involving its ability to convert novel inert secondary and tertiary amines into neuroactive substances with neurotransmitter properties, as a prerequisite for the treatment of neurological disorders of epilepsy, myoclonus, spinal spasticity, depressive illness and Parkinson’s disease.