Dopa-decarboxylase Inhibitors

Aromatic amino acid decarboxylase inhibitors (AAADIs), including carbidopa and benserazide, are competitive inhibitors of aromatic amino acid decarboxylase (AAAD) that do not penetrate brain. They have become a mainstay for anti-Parkinsonian therapy with levodopa. Prior to the advent of AAADIs, levodopa monotherapy was fraught with peripheral side effects due to peripheral conversion of levodopa to dopamine. Formulations of levodopa with AAADIs dramatically reduced these peripheral side effects without interfering with CNS efficacy, because the AAADIs do not penetrate the blood brain barrier at doses used clinically. The end-result was an increase in plasma levels and an increased entry of levodopa into brain, producing greater central efficacy with reduced peripheral side effects.