The Brain’s Dopamine Systems and Their Relevance to Restless Legs Syndrome

The family of catecholamines includes norepinephrine, epinephrine, and dopamine; of which dopamine is the most abundant in the central nervous system. It was not until the 1950s that dopamine was recognized as a critical neurotransmitter, and not simply an intermediate in the single biosynthetic pathway it shares with norepinephrine and epinephrine. In the first and rate-limiting step of the pathway, L-tyrosine is hydroxylated via the enzyme tyrosine hydroxylase (TH) to form L-dihydroxyphenylalanine (-DOPA) (1). Removal of a carboxyl group from L-DOPA by DOPA decarboxylase then produces dopamine. In subsequent steps, dopamine can then be further converted to norepinephrine and then to epinephrine by dopamine b-hydroxylase and phenylethanolamine-N-methyltrasferase, respectively (Fig. 1).