Brain monoamines and parkinsonism

Abstract

In Parkinson's disease there is a derangement of the metabolism of at least 3 major brain monoamines, namely, dopamine (DA), norepinephrine (NE) and serotonin (5-HT). Of these alterations the severe deficiency of DA in the striatum is most characteristic, being (a) found in Parkinsonian syndromes of any etiology and (b) significantly correlated with the degree of cell loss in the substantia nigra, and the severity of the main symptoms. On the basis of neurochemical-clinical correlations Parkinson's disease may be subdivided into (a) an asymptomatic stage during which the striatal DA deficiency may reach a marked degree but can be compensated by the remaining DA neurons, and (b) the stage of decompensation (i.e. clinically manifest disease) which ensues when the depetion of striatal DA reaches 70% or more. L-Dopa's main feature as a specific antiparkinson drug may be seen in its potential to revert the decompensated stage of the disease to the stage of functional compensation. This is in many cases possible because (a) the DA turnover in the remaining DA neurons is increased, providing for a high rate of formation (from L-dopa) and release of DA; (b) the "denervated" striatal receptors are supersensitive to DA; and (c) the newly-formed DA can be expected to reach a wide area of the striatum due to the high degree of divergence of the dopaminergic innervation. Compared with the striatal DA deficiency, the degree of NE and 5-HT decrease in the Parkinsonian brain is moderate. The decrease in NE may be due to the (moderate) cell loss in the locus coeruleus; at present no morphological basis for the lowering of brain 5-HT is known. The functional significance of the changes in brain NE may be an aggravation of akinesia. The decrease in brain 5-HT may be related to aspects of Parkinson's disease in turn related to affective behavior and mood.