Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase

Peripheral decarboxylase inhibitors (PDIs) prevent conversion of levodopa to dopamine in the blood by the enzyme aromatic L-amino acid decarboxylase (AADC). Alterations in enzyme activity may contribute to the required higher dosages of levodopa observed in many patients with Parkinson’s disease. We evaluated the effect of levodopa/PDI use on serum AADC enzyme activity. Serum AADC enzyme activity was evaluated in three independent cohorts of patients with Parkinson’s disease or parkinsonism (n = 301) and compared between patients on levodopa/PDI vs. patients not on this medication. AADC enzyme activity was elevated in 62% of patients on levodopa/PDI treatment, compared to 19% of patients not on levodopa/PDI (median 90 mU/L vs. 50 mU/L, p < 0.001). Patients with elevated AADC activity had longer disease duration and higher doses of levodopa/PDI. These findings may implicate that peripheral AADC induction could underlie a waning effect of levodopa, necessitating dose increases to maintain a sustained therapeutic effect.

Study of influence of ascorbic acid, reducing sugars and methyldopa on betalains content in Celosia cristata callus

Aim. The aim of the present work is to investigate the influence of reducing sugars, ascorbic acid and methyl DOPA as one of the DOPA decarboxylase inhibitors on total amount and spectrum of betalains in the callus culture of cockscomb Celosia cristata L. (Amaranthaceae). Methods. Tissue culture methods, analytical high-performance liquid chromatography (HPLC), spectrophotometry. Results. Adding of some reducing sugars (1 % of glucose, arabinose or rhamnose) to the media does not increase the total betalains content. Ascorbic acid at a concentration of 5 mM also does not significantly affect the amount of betalains, but considerably inhibit the callus growth. Moreover, ascorbic acid causes significant decreasing of the dopamine content and the normalized concentration of the main betacyanin pigment of the callus – amaranthin. Investigations have begun to study the effects of DOPA-decarboxylase inhibitors on the content of betalains and dopamine. Increased level of betalains in the callus in the presence of all used concentrations of methylDOPA was aobserved. The necessity of use of ascorbic acid or another stabilizer of methylDOPA in order to prevent oxidation of this inhibitor has been established. Conclusions. The data obtained suggest that methylDOPA as well as, probably, other inhibitors of DOPA decarboxylase can influence on betalains level in callus culture, so their use may be a potential strategy for these pigments content increasing. Keywords: Celosia cristata L. betalains, dopamine, callus culture.

The human experience with intravenous levodopa

Objective: To compile a comprehensive summary of published human experience with levodopa given intravenously, with a focus on information required by regulatory agencies. Background: While safe intravenous use of levodopa has been documented for over 50 years, regulatory supervision for pharmaceuticals given by a route other than that approved by the U.S. Food and Drug Administration (FDA) has become increasingly cautious. If delivering a drug by an alternate route raises the risk of adverse events, an investigational new drug (IND) application is required, including a comprehensive review of toxicity data. Methods: Over 200 articles referring to intravenous levodopa (IVLD) were examined for details of administration, pharmacokinetics, benefit and side effects. Results: We identified 142 original reports describing IVLD use in humans, beginning with psychiatric research in 1959-1960 before the development of peripheral decarboxylase inhibitors. At least 2781 subjects have received IVLD, and reported outcomes include parkinsonian signs, sleep variables, hormones, hemodynamics, CSF amino acid composition, regional cerebral blood flow, cognition, perception and complex behavior. Mean pharmacokinetic variables were summarized for 49 healthy subjects and 190 with Parkinson’s disease. Side effects were those expected from clinical experience with oral levodopa and dopamine agonists. No articles reported deaths or induction of psychosis. Conclusion: At least 2781 patients have received i.v. levodopa with a safety profile comparable to that seen with oral administration.