Analysis Of L-dopa Research Articles

Analysis of L-DOPA and droxidopa binding to human β2-adrenergic receptor

Over the last two decades, an increasing number of studies has been devoted to a deeper understanding of the molecular process involved in the binding of various agonists and antagonists to active and inactive conformations of β2-adrenergic receptor (β2AR). The 3.2 Å x-ray crystal structure of human β2AR active state in combination with the endogenous low affinity agonist adrenaline offers an ideal starting structure for studying the binding of various catecholamines to adrenergic receptors. We show that molecular docking of levodopa (L-DOPA) and droxidopa into rigid and flexible β2AR models leads for both ligands to binding anchor sites comparable to those experimentally reported for adrenaline, namely D113/N312 and S203/S204/S207 side chains. Both ligands have a hydrogen bond network that is extremely similar to those of noradrenaline and dopamine. Interestingly, redocking neutral and protonated versions of adrenaline to rigid and flexible β2AR models results in binding poses that are more energetically stable and distinct from the x-ray crystal structure. Similarly, lowest energy conformations of noradrenaline and dopamine generated by docking into flexible β2AR models had binding free energies lower than those of best poses in rigid receptor models. Furthermore, our findings show that L-DOPA and droxidopa molecules have binding affinities comparable to those predicted for adrenaline, noradrenaline, and dopamine, which are consistent with previous experimental and computational findings and supported by the molecular dynamics simulations of β2AR-ligand complexes performed here.

Development and Characterization of Oral <i>Mucuna pruriens</i> Seed Extract Jelly

The objective of this research was to develop Mucuna pruriens jelly formula to be suitable and easily edible for Parkinson’s patients. The recipe of jelly consisted of M. pruriens seed dry extract as an active ingredient, gelatin, glycerin, citric acid, sodium benzoate, steviol, coffee flavor, and purified water. The jelly was analyzed for physical and chemical characteristics by microscopy and UV-Vis spectrophotometry. It was found that pH of the M. pruriens jelly was 4.77. The microscopic characteristics showed that the jelly texture had a consistent distribution of various components (2.53 particles/cm2), with different particles sizes. The observation of the physical macroscopic characteristics found that M. pruriens jelly had dark brown color, smooth surface, and elastic texture, hence suitable for consumption. The analysis of physical stability by observing the changes of appearance with naked eyes for 4 weeks at 30 °C and 4 °C showed that M. pruriens jelly had physical stability at 4 °C better than at 30 °C. The chemical analysis of L-dopa by UV-Vis spectrophotometry revealed that M. pruriens jelly contained a sufficient amount of L-dopa i.e. 542 mg/piece. This research could be developed to be a health product for Parkinson’s patients by taking 2 pieces per day in the morning since the therapeutic dose for Parkinson’s disease is 1000 mg of L-dopa total/day (single dose in the morning).

Analysis of L-DOPA and Droxidopa Binding to Human Beta 2-Adrenergic Receptor

Over the last two decades, an increasing number of studies have been devoted to the understanding of the molecular mechanism involved in the binding of different agonists and antagonists to β2-adrenergic receptor (β2AR) inactive and active conformations. The active-state 3.2 Å X-ray crystal structure of the human β2AR in complex with the endogenous low affinity agonist adrenaline represents an optimal starting structure for the analysis of the binding of different catecholamines to adrenergic receptors.

Pharmacokinetic-Pharmacodynamic Modeling of Levodopa in Patients With Advanced Parkinson Disease

The aims of the present study were to investigate the pharmacokinetic and pharmacodynamic (pk/pd) relationship of levodopa (l-dopa) in patients with advanced Parkinson disease (PD) and also to evaluate the effect of tolcapone on the pk/pd analysis of l-dopa in 1 patient with severe dyskinesias and fluctuations. The pharmacokinetics (plasma concentrations of l-dopa and 3-O-methyldopa [3-OMD]) and motor effects (global score of the Unified Parkinson's Disease Rating Scale-III) of a single dose of l-dopa (plus the peripheral decarboxylase inhibitor 1:4) were determined in 14 patients with advanced PD. Patients were classified into 2 groups according to Hoehn and Yahr scale (stages 2 and 3). In 1 patient with severe dyskinesias and fluctuations, pk/pd of l-dopa were evaluated before and after coadministration of tolcapone at 100 mg 2 times daily for 1 month. The pk/pd analysis was based on an estimate of the maximal response model with a semiparametric approach to effect site equilibrium. The highest levels of l-dopa and 3-OMD were observed in patients with stage 3 of Hoehn and Yahr scale. We showed differences in the pk/pd parameters after coadministration of tolcapone in 1 patient as well as the clinical improvement.Univariate analysis showed some significant correlations (P < 0.05) between l-dopa pk/pd parameters and patients' age, duration of l-dopa treatment, and duration of the disease. Multivariate analysis adjusted for patients' age, sex, duration of the disease, and Hoehn and Yahr stage showed that presence of diphasic (dyskinesia-improvement-dyskinesia [DID]) dyskinesias was the only independent predictor of larger threshold level - EC50 (mean concentration at half maximal effect) of l-dopa (P = 0.034). The motor complications during long treatment therapy in patients with advanced PD especially with stage 3 Hoehn and Yahr scale were correlated to the higher plasma concentrations of l-dopa. In the presented study, patients with motor complications, especially with DID dyskinesias, exhibited a larger threshold level (EC50). The clinical improvement of a patient who received l-dopa and tolcapone can be explained by tolcapone-induced changes of peripheral and central l-dopa pharmacokinetics, which led to a decrease of l-dopa EC50 and 3-OMD concentrations. Our data indicate that pk/pd analysis may be helpful for monitoring the efficiency of therapeutic strategy applied in PD patients.

Determination of l-Dopa Content and Other Significant Nitrogenous Compounds in the Seeds of Seven Mucuna and Stizolobium Species in China

Seven samples of seeds from the genera Mucuna and Stizolobium (Leguminosae) were collected throughout southern China. HPLC analysis revealed l-dopa concentrations ranging from 3.9 to 6.2%. The seeds of the most commercially available species, S. pruriens var. utilis, collected biweekly during the fruit period, were also assayed using the same method, and their l-dopa concentrations were found to vary between 4.2 to 10.6%. Other nitrogenous compounds, which are significant in chemotaxonomy between the two plant types or have potential influence on analysis of l-dopa in the seeds were identified as stizolamine 3,4-dihydro-5-hydroxymethyl-4-methyl-3-oxopyrazinyl-guanidine), l-3-carboxy-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, and its derivatives.

UV Spectrophotometric Microdetermination of L-DOPA Based on Complex Formation with Copper(II)Ion

The UV spectrophotometric investigations obtained for the reaction between L-DOPA and copper(II)ion contribute to the clarification of equilibrium conditions of the complex formation both in the excess of metal ion and ligand. For the complex obtained in the excess of copper(II)ion optimum conditions were established, as well as the stoichiometric composition (1:1) and conditional stability constant logK' = 5.70±0.05. The proposed method, using copper(II)ion, as the analytical reagent in excess, for the UV spectrophotometric determination is suitable for accurate, sensitive and selective analysis of L-DOPA both in pure and dosage forms containing benzerazide.

Analysis Of l-dopa in pharmaceutical preparations and of total phenols content in urine by means of an enzyme—amperometric sensor

An enzyme—amperometric method is proposed for the analysis of total phenols and l-dopa; the method is based on the enzyme tyrosinase, which is immobilized in a Nylon membrane and coupled to an oxygen gas-diffusion amperometric electrode. The method was applied to the determination of total phenols in urine and to l-dopa in formulations and was evaluated as a promising alternative to currently adopted methods, e.g. to a classical spectrophotometric technique, chosen as a reference method.