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Purity: ≥98%
Levodopa (L-DOPA, Dopar, Sinemet, Pharmacopa, Atamet, Stalevo, Madopar, Prolopa) is the L-isomer of DOPA and the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) with anti-Parkinson's disease activity. It has been applied to alleviate Parkinson's disease symptoms. Levodopa is a chemical that is produced and utilized by humans, certain animals, and plants as part of their regular biology. L-tyrosine, an amino acid, is biosynthesised by certain humans and animals. Moreover, L-DOPA itself mediates the brain and central nervous system's release of neurotrophic factors.
Targets |
Dopamine receptor
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ln Vitro |
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ln Vivo |
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Cell Assay |
Levodopa, a dopamine (DA) precursor administered to patients with Parkinson's disease (PD), produces at 25-200 x 10(-6) M concentrations a dose-dependent reduction of 3H-DA uptake in foetal rat midbrain cultures. Also, a decrease in the number of viable cells and tyrosine hydroxylase (TH) positive neurones, plus disruption of the overall neuritic network are observed concurrently with an elevation of quinone levels in the culture medium. Ascorbic acid (AA), which abolished the quinone overproduction, partially prevented these effects. Though levodopa neurotoxicity in vivo is as yet unproven, AA may reduce vulnerability of endogenous or grafted DA neurones in patients with PD[1].
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Animal Protocol |
7-week-old C57BL/6J mice
20 mg/kg Orally Animal Surgery and Treatments. Wistar male rats (180–200 g, Iffa Credo) were anesthetized with pentobarbital (50 mg/kg, i.p.) and infused over 8 min with 6-OHDA (8 μg in 4 μl of 0.05% ascorbic acid in saline) at coordinates A = −3.8 mm, L = 1.5 mm, H = −8.5 mm. Three weeks later, they received twice a day, and for various periods of time, i.p. injections of vehicle, levodopa (in all experiments as l-DOPA methyl ester, 50 mg/kg, in combination with benserazide, a peripheral dopa decarboxylase inhibitor, 12.5 mg/kg) or levodopa plus SCH 23390 (0.5 mg/kg) or plus SKF 38393 (10 mg/kg), bromocriptine (10 mg/kg), quinpirole (0.1 mg/kg).[3] The majority of Parkinson's disease patients undergoing levodopa therapy develop disabling motor complications (dyskinesias) within 10 years of treatment. Stimulation of cannabinoid receptors, the pharmacological target of Delta 9-tetrahydrocannabinol, is emerging as a promising therapy to alleviate levodopa-associated dyskinesias. However, the mechanisms underlying this beneficial action remain elusive, as do the effects exerted by levodopa therapy on the endocannabinoid system. Although levodopa is known to cause changes in CB1 receptor expression in animal models of Parkinson's disease, we have no information on whether this drug alters the brain concentrations of the endocannabinoids anandamide and 2-arachidonylglycerol. To address this question, we used an isotope dilution assay to measure endocannabinoid levels in the caudate-putamen, globus pallidus and substantia nigra of intact and unilaterally 6-OHDA-lesioned rats undergoing acute or chronic treatment with levodopa (50 mg/kg). In intact animals, systemic administration of levodopa increased anandamide concentrations throughout the basal ganglia via activation of dopamine D1/D2 receptors. In 6-OHDA-lesioned rats, anandamide levels were significantly reduced in the caudate-putamen ipsilateral to the lesion; however, neither acute nor chronic levodopa treatment affected endocannabinoid levels in these animals. In lesioned rats, chronic levodopa produced increasingly severe oro-lingual involuntary movements which were attenuated by the cannabinoid agonist R(+)-WIN55,212-2 (1 mg/kg). This effect was reversed by the CB1 receptor antagonist rimonabant (SR141716A). These results indicate that a deficiency in endocannabinoid transmission may contribute to levodopa-induced dyskinesias and that these complications may be alleviated by activation of CB1 receptors.[4] Orally administered levodopa remains the most effective symptomatic treatment for Parkinson's disease (PD). The introduction of levodopa therapy is often delayed, however, because of the fear that it might be toxic for the remaining dopaminergic neurons and, thus, accelerate the deterioration of patients. However, in vivo evidence of levodopa toxicity is scarce. We have evaluated the effects of a 6-month oral levodopa treatment on several dopaminergic markers, in rats with moderate or severe 6-hydroxydopamine-induced lesions of mesencephalic dopamine neurons and sham-lesioned animals. Counts of tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra and ventral tegmental area showed no significant difference between levodopa-treated and vehicle-treated rats. In addition, for rats of the sham-lesioned and severely lesioned groups, immunoradiolabeling for TH, the dopamine transporter (DAT), and the vesicular monoamine transporter (VMAT2) at the striatal level was not significantly different between rats treated with levodopa or vehicle. It was unexpected that quantification of immunoautoradiograms showed a partial recovery of all three dopaminergic markers (TH, DAT, and VMAT2) in the denervated territories of the striatum of moderately lesioned rats receiving levodopa. Furthermore, the density of TH-positive fibers observed in moderately lesioned rats was higher in those treated chronically with levodopa than in those receiving vehicle. Last, that chronic levodopa administration reversed the up-regulation of D2 dopamine receptors seen in severely lesioned rats provided evidence that levodopa reached a biologically active concentration at the basal ganglia. Our results demonstrate that a pharmacologically effective 6-month oral levodopa treatment is not toxic for remaining dopamine neurons in a rat model of PD but instead promotes the recovery of striatal innervation in rats with partial lesions.[5] |
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References | ||
Additional Infomation |
L-dopa is an optically active form of dopa having L-configuration. Used to treat the stiffness, tremors, spasms, and poor muscle control of Parkinson's disease It has a role as a prodrug, a hapten, a neurotoxin, an antiparkinson drug, a dopaminergic agent, an antidyskinesia agent, an allelochemical, a plant growth retardant, a human metabolite, a mouse metabolite and a plant metabolite. It is a dopa, a L-tyrosine derivative and a non-proteinogenic L-alpha-amino acid. It is a conjugate acid of a L-dopa(1-). It is an enantiomer of a D-dopa. It is a tautomer of a L-dopa zwitterion.
Levodopa is a prodrug of dopamine that is administered to patients with Parkinson's due to its ability to cross the blood-brain barrier. Levodopa can be metabolised to dopamine on either side of the blood-brain barrier and so it is generally administered with a dopa decarboxylase inhibitor like carbidopa to prevent metabolism until after it has crossed the blood-brain barrier. Once past the blood-brain barrier, levodopa is metabolized to dopamine and supplements the low endogenous levels of dopamine to treat symptoms of Parkinson's. The first developed drug product that was approved by the FDA was a levodopa and carbidopa combined product called Sinemet that was approved on May 2, 1975. 3,4-Dihydroxy-L-phenylalanine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655). Levodopa is an Aromatic Amino Acid. View MoreLevodopa is a natural product found in Mucuna macrocarpa, Amanita muscaria, and other organisms with data available. Levodopa is an amino acid precursor of dopamine with antiparkinsonian properties. Levodopa is a prodrug that is converted to dopamine by DOPA decarboxylase and can cross the blood-brain barrier. When in the brain, levodopa is decarboxylated to dopamine and stimulates the dopaminergic receptors, thereby compensating for the depleted supply of endogenous dopamine seen in Parkinson's disease. To assure that adequate concentrations of levodopa reach the central nervous system, it is administered with carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, thereby diminishing the decarboxylation and inactivation of levodopa in peripheral tissues and increasing the delivery of dopamine to the CNS. Levodopa can cause developmental toxicity according to state or federal government labeling requirements. L-Dopa is used for the treatment of Parkinsonian disorders and Dopa-Responsive Dystonia and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. Peripheral tissue conversion may be the mechanism of the adverse effects of levodopa. It is standard clinical practice to co-administer a peripheral DOPA decarboxylase inhibitor - carbidopa or benserazide - and often a catechol-O-methyl transferase (COMT) inhibitor, to prevent synthesis of dopamine in peripheral tissue. The naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [PubChem] L-Dopa is the naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, L-Dopa can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. In particular, it is metabolized to dopamine by aromatic L-amino acid decarboxylase. Pyridoxal phosphate (vitamin B6) is a required cofactor for this decarboxylation, and may be administered along with levodopa, usually as pyridoxine. The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. Drug Tolerance: Levodopa therapy can have a dramatic effect on all the signs & symptoms of /Parkinson's Disease/. Early in the course of the disease, the degree of improvement in tremor, rigidity, & bradykinesia may be nearly complete. In early PD, the duration of the beneficial effects of levodopa may exceed the plasma lifetime of the drug, suggesting that the nigrostriatal dopamine system retains some capacity to store & release dopamine. A principal limitation of the long-term use of levodopa therapy is that, with time, this apparent "buffering" capacity is lost, & the patient's motor state may fluctuate dramatically with each dose of levodopa. A common problem is the development of the "wearing off" phenomenon; each dose of levodopa effectively improves mobility for a period of time, perhaps 1-2 hr, but rigidity & akinesia rapidly return at the end of the dosing interval. Increasing the dose & frequency of admin can improve this situation, but this often is limited by development of dyskinesias, excessive & abnormal involuntary movements. Dyskinesias are observed most often when the plasma levodopa concn is high, although, in some individuals, dyskinesias or dystonia may be triggered when the level is rising or falling. These movements can be as uncomfortable & disabling as the rigidity & akinesia of PD. In the later stages of PD, patients may fluctuate rapidly between being "off," having no beneficial effects from their medications, & being "on" but with disabling dyskinesias, a situation called to "on/off phenomenon." Pharmacodynamics: Levodopa is able to cross the blood-brain barrier while dopamine is not. The addition of a peripheral dopa decarboxylase inhibitor prevents the conversion of levodopa to dopamine in the periphery so that more levodopa can reach the blood-brain barrier. Once past the blood-brain barrier, levodopa is converted to dopamine by aromatic-L-amino-acid decarboxylase. Absorption: Orally inhaled levodopa reaches a peak concentration in 0.5 hours with a bioavailability than is 70% that of the immediate release levodopa tablets with a peripheral dopa decarboxylase inhibitor like carbidopa or benserazide. Route of Elimination: After 48 hours, 0.17% of an orally administered dose is recovered in stool, 0.28% is exhaled, and 78.4% is recovered in urine Volume of Distribution: 168L for orally inhaled levodopa. Clearance: Intravenously administered levodopa is cleared at a rate of 14.2mL/min/kg in elderly patients and 23.4mL/min/kg in younger patients. When given carbidopa, the clearance of levodopa was 5.8mL/min/kg in elderyly patients and 9.3mL/min/kg in younger patients. Metabolism / Metabolites: Levodopa is either converted to dopamine by aromatic-L-amino-acid decarboxylase or O-methylated to 3-O-methyldopa by catechol-O-methyltransferase. 3-O-methyldopa cannot be metabolized to dopamine. Once levodopa is converted to dopamine, it is converted to sulfated or glucuronidated metabolites, epinephrine E, or homovanillic acid through various metabolic processes. The primary metabolites are 3,4-dihydroxyphenylacetic acid (13-47%) and homovanillic acid (23-39%). Biological Half-Life: 2.3 hours for orally inhaled levodopa. Oral levodopa has a half life of 50 minutes but when combined with a peripheral dopa decarboxylase inhibitor, the half life is increased to 1.5 hours. Mechanism of Action: Levodopa by various routes crosses the blood brain barrier, is decarboxylated to form dopamine. This supplemental dopamine performs the role that endogenous dopamine cannot due to a decrease of natural concentrations and stimulates dopaminergic receptors. |
Molecular Formula |
C9H11NO4
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Molecular Weight |
197.19
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Exact Mass |
197.07
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Elemental Analysis |
C, 54.82; H, 5.62; N, 7.10; O, 32.46
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CAS # |
59-92-7
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Related CAS # |
L-DOPA-2,5,6-d3; 53587-29-4; L-DOPA-d6; 713140-75-1; L-DOPA sodium; 63302-01-2; L-DOPA-13C6; 201417-12-1; L-DOPA-13C; 586971-29-1
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PubChem CID |
6047
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Appearance |
White to off-white solid powder
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Density |
1.5±0.1 g/cm3
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Boiling Point |
448.4±45.0 °C at 760 mmHg
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Melting Point |
276-278 °C
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Flash Point |
225.0±28.7 °C
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Vapour Pressure |
0.0±1.1 mmHg at 25°C
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Index of Refraction |
1.655
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LogP |
-0.22
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tPSA |
103.78
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SMILES |
C1=CC(=C(C=C1C[C@@H](C(=O)O)N)O)O
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InChi Key |
WTDRDQBEARUVNC-LURJTMIESA-N
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InChi Code |
InChI=1S/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1
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Chemical Name |
(2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. (2). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: 3.33 mg/mL (16.89 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
 (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 5.0713 mL | 25.3563 mL | 50.7125 mL | |
5 mM | 1.0143 mL | 5.0713 mL | 10.1425 mL | |
10 mM | 0.5071 mL | 2.5356 mL | 5.0713 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT04990284 | Active Recruiting |
Drug: Opicapone Drug: L-DOPA/DDCI |
Parkinson Disease | Bial - Portela C S.A. | November 29, 2021 | Phase 4 |
NCT02480803 | Active Recruiting |
Device: deep brain stimulation Drug: Continuous intrajejunal infusion of levodopa-carbidopa |
Parkinson's Disease | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) |
December 19, 2014 | Phase 4 |
NCT03243552 | Active Recruiting |
Drug: L-DOPA versus Placebo Behavioral: Social Skills Training |
ASD | University of California, Los Angeles |
June 1, 2017 | Phase 2 |
NCT04469959 | Recruiting | Drug: L-Dopa Drug: Placebo |
Levodopa Gait Impairment |
Vanderbilt University Medical Center |
February 15, 2021 | Phase 2 |
NCT06075771 | Recruiting | Drug: Carbidopa Levodopa Drug: Placebo |
Anhedonia Depression |
Emory University | November 21, 2023 | Phase 4 |
Changes in D3 receptor binding elicited by repeated levodopa treatments of 6-OHDA-lesioned rats. Proc Natl Acad Sci U S A . 1997 Apr 1;94(7):3363-7. td> |
Progressive changes in D3-receptor binding and levodopa-induced rotations and neuropeptide mRNAs in CdPu of unilaterally 6-OHDA-lesioned rats following repeated treatment with levodopa and withdrawal. Proc Natl Acad Sci U S A . 1997 Apr 1;94(7):3363-7. td> |
Effects of nafadotride, a preferential D3-receptor antagonist on levodopa-induced rotations. Proc Natl Acad Sci U S A . 1997 Apr 1;94(7):3363-7. td> |