Dopamine is a monoamine oxidase B substrate in man

Abstract

DURING the past decade, the central neurotransmitter, dopamine (DA), has been much studied for it is known to be involved in certain human disease states, Parkinsonism¹ preeminently, and rather more inferentially, schizophrenia². DA is metabolised by monoamine oxidase (MAO)³, which catalyses the oxidative deamination of a wide range of monoamines^4,5, including the neurotransmitters noradrenaline (NA) and 5-hydroxytryptamine (5-HT), and other amines such as tyramine, tryptamine and phenylethylamine (PEA). On the basis of animal studies with the inhibitors, clorgyline⁶, and later deprenil⁷, MAO has been classified into two types, A and B. By definition, type A is selectively inhibited by clorgyline and type B by deprenil. In general, type A acts on 5-HT⁶ while type B prefers PEA⁸. In the rat, DA is preferentially deaminated by MAOA^9–11. It thus seemed paradoxical that, in the treatment of Parkinsonism, addition of the MAOB inhibitor, deprenil, to a DA-generating drug combination should produce further therapeutic benefit¹². In this report, we reconcile these apparently conflicting observations by demonstrating that, as far as DA oxidation is concerned, man may be different from rat: in two sites we have investigated, platelet and brain, DA is preferentially deaminated by an enzyme with the characteristics of MAOB.