Comparison of prodrugs L-DOPA and L-DOPS (droxidopa)

The top row shows the conversion of the prodrug L-DOPA (3,4-dihydroxy-L-phenylalanine, levodopa) to dopamine by aromatic L-amino acid decarboxylase (dopa-decarboxylase). The bottom row shows the conversion of L-DOPS (dl-dihydroxyphenylserine, droxidopa) to norepinephrine by the same enzyme. Both are simple decarboxylation reactions at the same part of the molecules. The only difference between L-DOPA (top left) and L-DOPS (bottom left) is that L-DOPS is hydroxylated at the carbon adjacent to the aromatic catechol moiety. The catecholamines dopamine (upper right) and norepinephrine (bottom right) differ by this same hydroxyl group. Under normal circumstances, dopamine can be concerted to norepinephrine by the enzyme dopamine beta-hydroxylase. This is not possible, however, in patients with dopamine beta-hydroxylase deficiency. Administering the synthetic prodrug L-DOPS (droxidopa) allows that blocked step to be bypassed, so that norepinephrine can be synthesized in vivo by decarboxylation. (Image by Dr. Douglas Lanska 2016.)