THE exact neurophysiological role of dopamine is still unclear, but it has been implicated in the functioning of the extra-pyramidal motor system (EPS)1,2. Experiments on animals and humans, however, indicate that the smooth functioning of the EPS depends on a fine balance between several biogenic amines3–5. Nevertheless, deficiencies of brain dopamine resulting from degeneration of the substantia nigra seem to be associated with the extrapyramidal symptoms of Parkinson's disease1–6. In accordance with these observations, attempts have been made to raise brain dopamine levels in patients suffering from Parkinsonism. Dopamine itself cannot be used, for it is incapable of crossing the blood-brain barrier, and therefore dopamine precursors, in particular L-3,4-dihydroxyphenylalanine (L-dopa), have been used7–10. Although such treatment apparently relieves the symptoms of hypokinesia, rigidity and posture, tremor is little affected and the necessity for large daily dosage and the side-effects of nausea and hypotension remain as serious drawbacks to the therapeutic use of L-dopa. Stock11 has recently suggested that 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine may be a potential anti-parkinsonism agent since this tyrosine hydroxylase cofactor may be deficient in patients suffering from Parkinsonism12.
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