Benserazide decreases central AADC activity, extracellular dopamine levelsand levodopa decarboxylation in striatum of the rat

In Parkinsonian patients treated with levodopa, peripheral decarboxylase in hibitors like carbidopa and benserazide are used to increase the central av ailability of levodopa. In experimental animal studies, this clinical situa tion is mimicked. However, at the dose used in many animal studies, both be nserazide and carbidopa pass the blood brain barrier. In this study, we inv estigated to what extent their presence in brain inhibits striatal aromatic amino acid decarboxylase activity. At 50 mg/kg i.p., both carbidopa and be nserazide decreased striatal decarboxylase activity. At l0mg/kg i.p., only benserazide decreased the enzyme activity, but this did not change extracel lular dopamine in striatum and allowed dopamine levels to increase after le vodopa administration. In contrast, the inhibition of central decarboxylase activity by 50mg/kg benserazide decreased striatal dopamine levels and pre vented the levodopa-induced increase. Therefore, it is important to careful ly consider the dose of the peripheral decarboxylase inhibitor used when th e central effects of levodopa are studied.