L-DOPA Solution Research Articles

L-DOPA coating improved phosphate glass fibre strength and fibre/matrix interface

The levodopa (L-DOPA) has been reported as a promising adhesive for various materials. In this study, we utilized L-DOPA as an interfacial agent for phosphate glass fibre/polycaprolactone (PGF/PCL) composites, with the aim to enhance the interfacial properties between the fibres and polymer matrix. The PGFs were dip-coated in varying concentrations of L-DOPA solution ranging between 5 and 40 g L-1. The fibre strength and interfacial shear strength (IFSS) of the composites were measured via a single fibre tensile test and single fibre fragmentation test, respectively. It was found that the L-DOPA agent (at conc. 10 g L-1) significantly improved the IFSS of the composites up to 27%. Also, the L-DOPA coating (at conc. 40 g L-1) significantly increased the glass fibre strength up to 18%. As a result, an optimum coating level could be tailored depending on application and whether fibre strength or IFSS was of greater importance. In addition, SEM and TGA analyses were used to detect and quantify the coating agents. FTIR and XPS further confirmed presence of the coating and indicated the zwitterionic crystals of L-DOPA and the formation of a melanin-like polymer layer. The spectroscopy data also evidenced that both catechol and amine groups contributed to the interaction between the L-DOPA and the PGF surface.

Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self-Healing Supramolecular Gel.

This paper reports the use of a self‐assembling hydrogel as a delivery vehicle for the Parkinson's disease drug l‐DOPA. Based on a two‐component combination of an l‐glutamine amide derivative and benzaldehyde, this gel has very soft rheological properties and self‐healing characteristics. It is demonstrated that the gel can be formulated to encapsulate l‐DOPA. These drug‐loaded gels are characterized, and rapid release of the drug is obtained from the gel network. This drug‐loaded hydrogel has appropriate rheological characteristics to be amenable for injection. This system is therefore tested as a vehicle for nasal delivery of neurologically‐active drugs—a drug delivery strategy that can potentially avoid first pass liver metabolism and bypass the blood–brain barrier, hence enhancing brain uptake. In vitro tests indicate that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrate that the nasal delivery of a gel loaded with 3H‐labeled l‐DOPA out‐performed a simple intranasal l‐DOPA solution. This is attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It is demonstrated that the likely routes of brain penetration of intranasally‐delivered l‐DOPA gel involve the trigeminal and olfactory nerves connecting to other brain regions.

Zwitterion-Modified Ultrafiltration Membranes for Permian Basin Produced Water Pretreatment

Unconventional oil and gas extraction generates large quantities of produced water (PW). Due to strict environmental regulations, it is important to recover and reuse PW. In this study, commercial polyethersulfone (PES) ultrafiltration (UF) membranes were surface-modified with zwitterionic polymer 3-(3,4-Dihydroxyphenyl)-l-alanine (l-DOPA) solution to alleviate membrane fouling during the ultrafiltration of shale oil PW of the Permian Basin. UF membranes were coated in l-DOPA solution by using a dip coating technique. Membrane characterization tests confirmed successful l-DOPA coating on UF membranes. While performing the experiments, permeate flux behaviors of the uncoated and coated membranes and antifouling resistance of the zwitterionic coating were evaluated. Among the coated UF membranes with varying coating times from one day to three days, the three-day coated UF membrane showed a good flux performance and the highest fouling resistance. The flux reduced by 38.4% for the uncoated membrane, while the reduction was 16% for the three-day coated membrane after the 5 h ultrafiltration of PW. Both improvements of the flux performance and recovery ratio are attributed to a negatively-charged surface developed on the membranes after the zwitterionic coating. The UF pretreatment also improved the flux behavior of the later forward osmosis (FO) process for PW treatment.

Enhancing the bioactivity of yttria-stabilized zirconia immobilized with adhesive peptide using l-dopa as cross-linker

To resolve the disadvantages of the bio-inert nature of zirconia ceramics and their poor bonding to bone tissue, surface modification to enhance tissue integration usually has to be performed. In this study, we developed a simple, efficient, and organic solvent-free biomimetic modified strategy through the use of l-dopa, which is known to have strong adhesive behavior, as a cross-linker for immobilization with adhesive peptide. 3Y-TZP was first immersed into l-dopa solution to form a strongly adhesive coating. RGD peptides were then immobilized onto the l-dopa-grafted surface. Several characterization analyses, including static contact angle measurement, FTIR spectroscopy, and Bradford staining, showed that RGD peptides were successfully immobilized onto the 3Y-TZP surface through the l-dopa linker. In vitro assay revealed that a significant increase in MG-63 osteoblast cell attachment, proliferation, and differentiation was observed from SEM, WST-1, and ALP activity on the l-dopa-grafted 3Y-TZP surface with the immobilized adhesive peptide. Thus, the results of this study suggest that l-dopa can be used as a cross-linker to immobilize adhesive peptides onto a 3Y-TZP surface and further enhance bioactivity.

Analysis of l-DOPA-derived melanin and a novel degradation product formed under alkaline conditions

When the therapeutic drug l-DOPA, which is used to treat Parkinson’s disease, is combined with magnesium oxide (MgO), a formulation change produces a dark substance. Infrared spectroscopy reveals that this substance is melanin. After allowing the l-DOPA and MgO mixture to stand, the l-DOPA content decreases significantly, and a new degradation product (the final degradation product of l-DOPA, FDP-D) is generated. Formation of this product requires a solution with a pH of >10, and the presence of MgO is not necessary. FDP-D is not produced by tyrosinase decomposition of l-DOPA and is therefore not a melanin-related compound. Pure FDP-D is isolated by adjusting the l-DOPA solution to pH 10 with ammonium hydroxide, allowing it to stand for 3 days at room temperature, adding trifluoroacetic acid (TFA), filtering the precipitate, and separating the supernatant with high-performance liquid chromatography (HPLC). Mass spectrometry indicates that the isolated FDP-D has a molecular formula of C9H9NO7. On the basis of NMR analysis (1H NMR, 13C NMR, DEPT, H-H COSY, HMQC, and HMBC), FDP-D appears to be a substance with the novel structure 7a-hydroxy-5-oxo-1,2,3,5,7,7a-hexahydropyrano [3,4-b]pyrrole-2,7-dicarboxylic acid.

Morphology of synthetic DOPA-eumelanin deposited on glass and mica substrates: An atomic force microscopy investigation

Bright field microscopy and atomic force microscopy techniques are used to investigate morphological properties of synthetic eumelanin, obtained by oxidation of l-DOPA solution, deposited on glass and mica substrates. Deposits of eumelanin are characterized by aggregates with different shape and size. On a micrometric scale, filamentous as well as granular structures are present on glass and mica substrates, with a larger density on the former than on the latter. On a nanometric scale, filamentous aggregates, several microns long and about 100nm wide and high, and granular aggregates, ∼50nm high and 100nm wide, are found on both substrates, whereas point-like deposits less than 10nm high and less than 50nm wide are found on mica substrate. Dynamic light scattering measurements and atomic force microscopy images support the evidence that eumelanin presents only nanometric point-like aggregates in aqueous solution, whereas such nanoaggregates organize themselves according to granular and filamentous structures when deposition occurs, as a consequence of interactions with the substrate surface.

A standardised protocol for measuring phenoloxidase and prophenoloxidase in the honey bee, Apis mellifera

The prophenoloxidase activating system (ProPO-AS) is an integral part of the constitutive in- nate immune response in insects, the products of which are commonly assayed to assess an individual's ability to respond to immune challenges. However, there is considerable variation in the methodologies associated with these assays, and as such, it is not always clear how to interpret results. We have optimised assays for measuring phenoloxidase in its active (PO) and zymogen (ProPO) forms in the honey bee, Apis mellifera. Contrary to results for other insects, we found that the activator α-chymotrypsin, when used at a low concentration (0.5 mg mL −1 ), combined with a minimal activation time (5 min), provided optimal conditions for assaying ProPO. In addition, a saturated L-dopa solution was required for assaying both PO and ProPO. The results highlight the importance of defining the working parameters of each assay to be species-specific. honey bee / Apis mellifera / phenoloxidase / innate immunity / activator

Screening of porous and cellular materials for covalent immobilisation of Agaricus bisporus tyrosinase

We conducted a systematic study of covalent immobilisation of Agaricus bisporus tyrosinase onto typical enzyme carriers. Acrylic beads, two commercial silica gels with different pore structures and mesoporous silica foam (MCFs) beads functionalised using different organosilanes showed that only aminated MCFs offer active preparations with immobilisation efficiencies greater than 100% and a similar ratio of diphenolase (L-DOPA) to monophenolase (L-tyrosine) activities as the free enzyme. The native enzyme was entirely inactivated during incubation at 55°C for 30 min, whereas the enzyme immobilised on acrylic carrier or MCF retained 46 and 35%, respectively, of the initial activity after similar treatment. Susceptibility of native and immobilised tyrosinase to suicide inactivation in the presence of L-tyrosine and L-DOPA was tested in repeated batch tests. However, none of the preparations obtained in the L-DOPA solution was operationally stable enough to be used for practical applications.

Carbon nanotubes paste electrodes modified with a melanic polymer: Analytical applications for the sensitive and selective quantification of dopamine

This work describes the advantages of carbon nanotubes paste electrodes (CNTPE) modified with a melanic polymer for the highly sensitive and selective quantification of dopamine. The polymer is electrogenerated from a 3.0 × 10 −3 M l-dopa solution (in a 0.050 M phosphate buffer pH 7.40) by applying 0.80 V for 120 min. Two strategies for dopamine quantification are described, the amperometric detection at 0.200 V using 1.0 × 10 −3 M ascorbic acid in the measurement solution to improve the sensitivity of the assay; and the adsorptive stripping detection with medium exchange using differential pulse voltammetry (DPV) as transduction mode. Detection limits of 2.0 nM and 20 nM were obtained with amperometry and adsorptive stripping, respectively. The interference of 5.0 × 10 −4 M ascorbic acid and 5.0 × 10 −5 M dopac was really negligible in both cases, demonstrating the advantages of the melanic polymer as permselective layer.

Reconsideration of phenoloxidase activity determination in white shrimp Litopenaeus vannamei

Though phenoloxidase (PO) activity has been used as an important index in immunological research of crustaceans, methods for the determination of PO activity are not consistent even for the same species. Plasma, the major location of PO activity, should be the most reasonable sample, instead of hemocytes or serum, for the determination of PO activity of shrimp. The current study provided a thorough characterization and reconsideration for PO activity assay in the plasma of Litopenaeus vannamei. Results show that the final concentration of l-dihydroxyphenylalanine ( l-DOPA) for PO activity assay should be no less than 1.5 mg ml −1, and pH 6.6 should be used to maintain the stability of l-DOPA solution. This study provides direct evidence that PO activity is significantly inhibited by EDTA, and it is suggested to use EDTA-free anticoagulant in separating plasma for PO activity assay in future studies. Repeated measurements indicated that the assayed PO activities are significantly affected by preservation conditions, and plasma is quite unstable with spontaneous activation when put in ice or stored at −20 °C. Thus samples need to be measured immediately or preserved at −80 °C with assay as soon as possible after it is thawed, and should not be preserved for a second time for measuring PO activity.

Behavioural effects of a selective NMDA NR1A/2B receptor antagonist in rats with unilateral 6-OHDA + parafascicular lesions

Experimental lesions involving the parafascicular (Pf) nucleus and medial forebrain bundle (MFB) may model to some extent the pathological loss of glutamatergic neurons from the centromedian–parafascicular (CM–Pf) complex and nigral dopaminergic cell loss observed clinically at post-mortem in Parkinson's disease (PD) cases. Our study investigated whether there were alterations in symptomatology in such rats with unilateral 6-OHDA + Pf lesions after treatment with either a selective NR1A/NR2B NMDA antagonist and/or l-dopa. Rats were given dual surgery to the MFB with 6-hydroxydopamine (6-OHDA) and Pf with N-methyl- d-aspartate (NMDA). (i) An NR1A/NR2B selective NMDA antagonist (BZAD-01; 10 mg/kg), (ii) l-dopa (25 mg/kg), (iii) BZAD-01 + l-dopa (10 mg/kg; 25 mg/kg) or (iv) vehicle solution were administered for 6 weeks, during which behavioural testing was performed. BZAD-01 improved postural asymmetry in the first month as well as apomorphine-induced rotation. The latter was also improved by l-dopa in this model. These data support the use of selective NR1/NR2B NMDA antagonists in the therapeutics of PD.

Changes in Chemical Structure and Biological Activity of L-DOPA as Influenced by an Andosol and Its Components

Velvetbean (Mucuna pruriens) has been reported to release 3-(3′,4′-dihydroxyphenyl)-L-alanine (L-DOPA) as an allelochemical that inhibits the growth of other plants, although the inhibitory activity depends on the soil type and it is extremely reduced in Andosols. To clarify the effects of Andosols and their components on the chemical structure and plant-growth-inhibitory activity of L-DOPA, an L-DOPA solution was reacted with an Andosol and its components (weathered pumice and purified allophane), and the resultant solution was subjected to 1H nuclear magnetic resonance and ultraviolet-visible spectral analyses, and plant-growth-inhibitory activity tests. When the L-DOPA solution was added to the soil components, the concentration of L-DOPA in the solution decreased by adsorption and transformation (polymerization) reactions. The adsorption mechanism included a ligand exchange reaction. The rate of L-DOPA transformation was faster at higher pH values. The soil components displayed a catalytic activity and accelerated the transformation of L-DOPA. Similar transformation occurred when light was irradiated. At pH values higher than 4.0, the transformed products from L-DOPA consisted of humic substances-like heterogeneous components, whereas specific components with low molecular weight were included when L-DOPA was transformed at a pH value of 9.7 or higher. The plant-growth-inhibitory activity of L-DOPA was extremely weakened when L-DOPA was adsorbed on or transformed (polymerized) by soil components. Therefore, in soils with high abilities of adsorption and transformation of L-DOPA such as in Andosols, it was likely that the L-DOPA concentration in the soil solution decreased quickly by adsorption and transformation reactions and the allelopathic activity of L-DOPA was lost.

Reexamination of phenoloxidase in larval circulating hemocytes of the silkworm, Bombyx mori

We have developed a modified method to detect phenoloxidase activity on hemocytes by using freshly prepared l-DOPA (1 mg/ml in 35% ethanol) to fix and incubate larval hemocytes. This method is more sensitive than the common method, in which hemocytes were fixed in 4% formaldehyde and then incubated with 2 mg/ml l-DOPA in water separately. Phenoloxidase assayed using this modified method can be inhibited by phenyltiourea (phenoloxidase inhibitor). After incubation with l-DOPA solution in ethanol, most prohemocytes, all plasmatocytes and young granulocytes are stained brown due to oxidation of l-DOPA into pigments, indicating that they have phenoloxidase. Oenocytoids are dimly stained because many of their cell inclusions have been released during the treatment. Large propidium-iodide-negative prohemocytes have strong phenoloxidase activity and are easily misunderstood as propidium-iodide-positive oenocytoids if the fluorescent method is not used for identification. Thus, in addition to oenocytoids and plasmatocytes, some prohemocytes and granulocytes in the silkworm also have phenoloxidase.

Oral l-dopa solution therapy of menstrual-related fluctuations in Parkinson's disease

In 1986 Quinn and Marsden reported menstrual-related fluctuations in women with Parkinson’s disease (PD) [1]. There have been other reports of this phenomenon, but almost all of them are in abstract form [2–6]. However, their cause remains unclear and only a few treatments have been recommended [2,4]. We present a perimenopausal PD patient whose perimenstrual motor fluctuations showed a good response to an oral L-dopa solution taken hourly. A 50 year-old woman who had been diagnosed with PD at the age of 40 presented with right-hand tremor and stiffness. She had been treated for 1 year with carbidopa/Ldopa, amantadine and selegiline, with an excellent response. At the age of 44 she suffered severe motor fluctuations, wearing-off phenomenon and peak-dose dyskinesia; she was currently taking 500 mg of L-dopa a day in five divided doses of 100 mg. Four years later, coinciding with the onset of her menopause, she experienced a progressive worsening of all the parkinsonian symptoms around the time of her menses. These fluctuations proved to be refractory to any therapy applied and the patient was admitted to hospital for assessment. We noted that, starting at day 19 of her menstrual cycle and for the next 5–6 days her parkinsonian symptoms were much worsened, with off-periods up to 10 h/day and an UPDRS while ‘off’ of 62; after menstruation and for 18 days her off periods lasted 2 h/day. When she was not in a menstrual period her UPDRS ‘on’ was 16, but when she was examined around the time of her menstrual period, her UPDRSS on was 25. Conventional therapy with L-dopa (700 mg/day), bromocriptine (40 mg/day) and selegiline (10 mg/day) was not effective in controlling the menstrual parkinsonian fluctuations despite increasing the frequency of dosage of L-dopa and bromocriptine. She did, however, note a substantial improvement when taking a Ldopa/carbidopa/ascorbic acid solution orally at hourly intervals (13 intakes/day). Seven and a half tablets of Sinemet 25/100 and 2 g of crystaline ascorbic acid (vitamin C, Redoxon) were dissolved to 1 l of water to give a solution of 0.75 mg/ml levodopa, 0.185 mg/ml carbidopa, and 2 mg/ml ascorbic acid (so the patient took, 76.9 ml/h of the solution, i.e. 57.6 mg of L-dopa/h). She started this treatment 5 days before her period, continuing throughout it and for 5 days after. Bromocriptine and selegiline were kept unchanged. The day she finished her period she returned to conventional treatment with L-dopa tablets. On this regimen her menstrual-related fluctuations improved dramatically and she experienced only 2 h off for a day and her UPDRS while this off was much less severe (UPDRS 22). Her on periods also improved on this regimen and the on UPDRS, during the menstrual period, was 18. PD usually begins between 50 and 60 years of age, but its incidence increases with age with a peak between 60 and 64 years of age [7]. Menopause onset occurs about 51 years of age and can last for 10–15 years [8]. Therefore, the majority of women suffer the onset of PD when they are climateric. That is why the number of parkinsonian menstruating women is low and the cyclic changes in their parkinsonian symptoms are not well recognized. Indirect clinical evidence suggests that estrogens may influence the course of the disease because menstrual worsening coincides with a presumed nadir in both estrogen and progesterone levels, and it is known that estrogens can modify the activity of the mesoestriatal, mesolimbic and mesocortical dopaminergic pathways both biochemically and behaviorally The only study that has examined the issue of parkinsonian motor symptoms and menstrual pattern in a meticulous and systematic manner, however, did not find a direct relationship between hormonal menstrual fluctuations and those of PD [6]. On the other hand, several studies suggest that

Amperometric Quantification of Dopamine Using Different Carbon Electrodes Modified with a Melanin-Type Polymer

The analytical performance of different carbon materials (glassy carbon, glassy carbon paste, graphite, graphite paste, carbon fiber and screen printed electrodes) modified with a melanic polymer is evaluated in connection with the quantification of dopamine. The electropolymerization was performed from a 3.0 × 10−3 M l-dopa solution (in a 0.050 M phosphate buffer pH 7.40) by applying 1.00 V for 60 min. The response of the polymer-modified carbon electrodes demonstrated to be very dependent on the nature of the carbon material, glassy carbon being the best. By using 1.0 × 10−3 M AA in the measurement solution, detection limits of 5.0 and 10.0 nM were obtained with a melanin-type polymer modified glassy carbon and carbon fiber electrodes, respectively. The interference of 5.0 × 10−4 M ascorbic acid and 5.0 × 10−5 M dopac at the melanin-type polymer modified glassy carbon electrode, was 7.0 and 3.0%, respectively. A comparison between a glassy carbon electrode modified with a commercial melanin and a glassy carbon electrode modified with the electrogenerated melanic polymer showed that the permselective properties are similar, although the rejection of anions is less effective in the case of the commercial melanin.

Transdermal Absorption of L-Dopa from a New System Composed of two Separate Layers of L-Dopa and Hydrogel in Rats

To maintain the stability of L-dopa in hydrogel, a new system composed of two separate layers of L-dopa and hydrogel was developed. L-Dopa sheets were made by immersing L-dopa solution into wiper sheets and by lyophilizing them. Examination for stability of L-dopa in the L-dopa sheet revealed that its stability was maintained for at least 12 weeks, providing the sheet was kept at room temperature in a dark box. In a cutaneous absorption study of L-dopa in rats, an L-dopa sheet was attached to the shaved abdominal skin. A hydrogel composed of cutaneous absorption enhancers, water and ethanol, was spread on vinyl tape (hydrogel sheet), and this sheet was placed over the L-dopa sheet. L-Dopa that was administered transdermally effectively penetrated through the skin: The plasma level of L-dopa peaked at 30 min and remained high between 60 and 180 min after the cutaneous application. Our system, composed of two separated layers of L-dopa and hydrogel, enabled the stability of L-dopa to be maintained without losing transdermal absorption of L-dopa.

Melanocytes in the stria vascularis and vestibular labyrinth of the Mongolian gerbil (Meriones unguiculatus).

Inner ear melanocytes are mainly present in the cochlea, vestibular organ, and endolymphatic sac, but their exact biological function has not been determined. In this investigation, we study the pigment cells in the membranous labyrinth of the gerbil. The inner ear melanocytes of M. unguiculatus show an irregular dendritic shape with cytoplasmic processes. These cells are disposed following the distribution of strial marginal and vestibular dark cells that have an important metabolic activity. Gerbil inner ear melanocytes are characterized by the presence of melanosomes, which are homogeneously dense organelles, of variable size and shape, that are surrounded by a membrane. In these cells, the Golgi apparatus plays a important role in melanin synthesis. When melanocytes were incubated in L-DOPA solution, the vesicles and cisterns of the Golgi apparatus exhibited a positive tyrosinase reaction. An interesting observation is the relation between melanocytes and inner ear capillaries. Sometimes, near to sensory vestibular areas, the melanocytes were in contact with Schwann cells and with myelinated fibres of vestibular nerve. The ultrastructural findings of this investigation are consistent with the hypothesis that melanocytes may have functional significance in the inner ear.

Circular dichroism and ultraviolet studies of the cupric(II)- and nickel(II)- l-3,4-dihydroxyphenylalanine complex

Extrinsic circular dichroism (CD) spectra in the wavelength region 200–600 nm were clearly exhibited by coexistent solutions of Cu(II) or Ni(II) and l-3,4-dihydroxyphenylalanine ( l-DOPA) in 10 mM phosphate buffer (pH 7.4) at 36°C. The Cu(II)- l-DOPA complexes in the buffer were not affected by the oxidative reaction, were slowly dissociated, and then simulataneously reformed into new optically inactive complexes in proportion to the incubation time. The addition of poly- l-lysine (PLL) to the Cu(II)- l-DOPA solution indicated the presence of the oxidative product of DOPA quinone under the same conditions. The formation of Ni(II)- l-DOPA complexes, on the other hand, was a two-step process and, coexistence with PLL in the solution showed the same result as noted in the case of Cu(II). The effect of PLL on the oxidation of l-DOPA was much more secondarily structurally selective than asymmetrically selective.

Chronic haloperidol

To analyse the mechanisms underlying chronic effects of antipsychotic drugs, a simpler invertebrate preparation is proposed. Bathing of leeches for three days in a 1.0 microM aqueous haloperidol (HAL) solution resulted in (i) discoordination of locomotion, including the inability of the posterior sucker to successfully attach to the substratum, and (ii) transmitter depletion in all putative dopamine (DA) neurones of the sucker and in some, but not all, DA neurones of middle body segments. Both behavioural restoration and cellular DA recovery were observed in disabled animals after bathing in 1.25 mM L-DOPA solution. We conclude that chronic HAL-produced motor disorders are causally related to DA deficiency.

Continuous oral administration of L-dihydroxyphenylalanine (L-DOPA) solution to patients with advanced Parkinson's disease.

In six patients with advanced Parkinson's disease (PD), we have characterized the clinical responses and serum levels of DOPA and 3-O-methyldopa in response to continuous i.v., nasogastroduodenal (NGD), and oral (p.o.) administration of L-DOPA solution with concomitant suppression of peripheral decarboxylase activity by carbidopa. When compared to therapy with L-DOPA/carbidopa tablets, all patients experienced increased "on" and decreased "off" time with continuous L-DOPA intake. This improvement in mobility was accompanied by increases in duration and severity of dyskinesias. Serum levels of DOPA and 3-O-methyldopa were linearly related in ultrafiltered serum water compared to perchloric acid-treated serum samples, suggesting little protein binding. DOPA serum levels at which patients first turned "on" and those after several hours of continuous i.v. infusion clustered over a narrow range and were not predictable based on i.v. infusion rates, in spite of concomitant carbidopa intake. Continuous p.o. intake of L-DOPA solution produced serum levels of both DOPA and 3-O-methyldopa that were generally steady over the day and predictable based on L-DOPA intake rate. We conclude that "continuous" intake of L-DOPA solution orally, while cumbersome to and demanding of patients, can produce stable DOPA serum levels and approximate the improvement seen with continuous i.v. infusion. In our study, the apparent volume of distribution of L-DOPA was predictable with p.o. intake but not with i.v. administration of L-DOPA solution.