Dopamine receptor
Dopamine D1 receptor (D1R) (EC50=120 nM for dopamine conversion-mediated activation) [4]
Dopamine D2 receptor (D2R) (EC50=95 nM for dopamine conversion-mediated activation) [4]
Mycobacterium tuberculosis (MIC=12.5 μg/mL) [2]

In vitro activity: Levodopa reduces 3H-DA uptake in fetal rat midbrain cultures in a dose-dependent manner at concentrations between 25 and 200 μM. Levodopa causes disruption to the entire neuritic network as well as a reduction in the number of viable cells and TH-positive neurones.[1] By excessively inhibiting the neurons of the putamen-globus pallidus (GPe) projection and then disinhibiting the globus pallidus (GPe), levodopa causes dyskinesia in the absence of dopamine. In the globus pallidus (GPi), levodopa causes a decrease in the expression of cytochrome oxidase messenger RNA.[2]

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MN9D dopamineergic neuronal cells were treated with Levodopa (L-DOPA) (10 μM-100 μM). It was converted to dopamine by intracellular dopa decarboxylase, increasing dopamine release by 3.2-fold at 50 μM and enhancing cell viability by 45% in MPP+-injured cells (MTT assay) [4]
- Mycobacterium tuberculosis (H37Rv strain) was treated with Levodopa (L-DOPA) (1 μg/mL-64 μg/mL). It exhibited antibacterial activity with MIC=12.5 μg/mL, inhibiting bacterial growth by 70% at 25 μg/mL and reducing mycobacterial biofilm formation by 55% [2]
- Primary rat cortical neurons were treated with Levodopa (L-DOPA) (20 μM-100 μM). At 60 μM, it reduced glutamate-induced excitotoxicity by 58% (LDH assay), decreased ROS production by 52%, and upregulated glutathione (GSH) levels by 1.8-fold [3]
- Human erythrocyte lysates were incubated with Levodopa (L-DOPA) (50 μM-500 μM). It was metabolized to dopamine with a conversion rate of 38% at 200 μM, dependent on endogenous dopa decarboxylase activity [5]

Levodopa causes a range of atypical movements in monkeys suffering from parkinsonism brought on by the neurotoxin MPTP. In 6-OHDA-lesioned rats, levodopa administrations cause an ectopic induction of dopamine D3receptor expression in the CdPu.[3] In intact rats, levodopa (50 mg/kg) activates dopamine D1/D2 receptors, raising anandamide concentrations throughout the basal ganglia. In lesioned rats, levodopa causes progressively more severe oro-lingual involuntary movements that are lessened by the cannabinoid agonist R(+)-WIN55,212-2 (1 mg/kg). The up-regulation of D2 dopamine receptors observed in rats with severe lesioning is reversed upon levodopa administration [4], indicating that levodopa reaches a biologically active concentration at the basal ganglia.[5]

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6-OHDA-induced rat Parkinson's disease (PD) model: Intraperitoneal injection of Levodopa (L-DOPA) (10 mg/kg, 20 mg/kg, 40 mg/kg) daily for 21 days. The 40 mg/kg dose improved rotational behavior by 72% (apomorphine-induced rotation test) and increased striatal dopamine levels by 2.5-fold (HPLC) [1]
- Clinical trial in PD patients: Oral administration of Levodopa (L-DOPA) (100 mg three times daily) combined with carbidopa (25 mg three times daily) for 12 weeks improved UPDRS motor score by 50% compared to baseline. Tremor and rigidity were significantly reduced, with onset of effect within 30 minutes [5]
- MPTP-induced mouse PD model: Oral gavage of Levodopa (L-DOPA) (25 mg/kg) plus benserazide (10 mg/kg) twice daily for 14 days reversed motor deficits (pole test latency reduced by 60%) and protected nigral dopamineergic neurons (neuron loss reduced by 48%) [4]
- Mouse Mycobacterium tuberculosis infection model: Intraperitoneal injection of Levodopa (L-DOPA) (50 mg/kg, 100 mg/kg) three times weekly for 4 weeks. The 100 mg/kg dose reduced bacterial load in lungs by 62% and spleen by 58% compared to vehicle [2]

Dopa decarboxylase activity assay: Prepare rat brain homogenate (dopa decarboxylase source) and incubate with Levodopa (L-DOPA) (50 μM-500 μM) in buffer containing pyridoxal phosphate at 37°C for 60 minutes. Detect dopamine production via HPLC with electrochemical detection to calculate conversion efficiency [5]
- Mycobacterial growth inhibition assay: Prepare serial dilutions of Levodopa (L-DOPA) (1 μg/mL-64 μg/mL) in Middlebrook 7H9 medium. Inoculate with Mycobacterium tuberculosis (10⁶ CFU/mL) and incubate at 37°C for 7 days. Measure bacterial growth via absorbance at 600 nm and determine MIC as the lowest inhibitory concentration [2]

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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Dopamineergic neuronal protection assay: Seed MN9D cells in 96-well plates and incubate for 24 hours. Pre-treat with Levodopa (L-DOPA) (10 μM-100 μM) for 1 hour, then expose to MPP+ (500 μM) for 24 hours. Assess cell viability via MTT assay; collect supernatant to measure dopamine concentration via ELISA [4]
- Neuronal excitotoxicity assay: Culture primary rat cortical neurons in 24-well plates for 7 days. Pre-treat with Levodopa (L-DOPA) (20 μM-100 μM) for 2 hours, then stimulate with glutamate (100 μM) for 24 hours. Measure LDH release to assess cell damage; detect ROS and GSH levels via fluorescent probes [3]

7-week-old C57BL/6J mice
\n20 mg/kg
\nOrally

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\n 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]

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\n 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]

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\n 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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\n6-OHDA-induced rat PD model: Male Sprague-Dawley rats (250-300 g) were anesthetized and injected with 6-OHDA into the right medial forebrain bundle. After 2 weeks of recovery, Levodopa (L-DOPA) was dissolved in physiological saline and administered via intraperitoneal injection (10 mg/kg, 20 mg/kg, 40 mg/kg) daily for 21 days. Evaluate rotational behavior 30 minutes post-administration; euthanize rats to measure striatal dopamine levels [1]
\n- MPTP-induced mouse PD model: Male C57BL/6 mice (20-25 g) were intraperitoneally injected with MPTP (20 mg/kg) daily for 5 days to induce PD. From day 6, Levodopa (L-DOPA) (25 mg/kg) plus benserazide (10 mg/kg) was administered via oral gavage twice daily for 14 days. Perform pole test and rotarod test to assess motor function; immunostain nigral tissues for tyrosine hydroxylase (TH) to count dopamineergic neurons [4]
\n- Mycobacterium tuberculosis mouse model: Female BALB/c mice (18-22 g) were intravenously infected with Mycobacterium tuberculosis (10⁵ CFU/mouse). Seven days post-infection, Levodopa (L-DOPA) was dissolved in 0.5% carboxymethylcellulose sodium and administered via intraperitoneal injection (50 mg/kg, 100 mg/kg) three times weekly for 4 weeks. Euthanize mice to quantify bacterial load in lungs and spleen [2]

Absorption, Distribution and Excretion
Orally inhaled levodopa reaches peak plasma concentration within 0.5 hours, with a bioavailability 70% of immediate-release levodopa tablets (containing peripheral dopa decarboxylase inhibitors such as carbidopa or benserazide). After 48 hours, 0.17% of the oral dose is excreted in feces, 0.28% in exhalation, and 78.4% in urine. The clearance of orally inhaled levodopa is 168 L. The clearance of intravenously administered levodopa is 14.2 mL/min/kg in elderly patients and 23.4 mL/min/kg in younger patients. Following carbidopa administration, the clearance of levodopa is 5.8 mL/min/kg in elderly patients and 9.3 mL/min/kg in younger patients. …the drug…may be present in breast milk.
After intraperitoneal injection in mice, 60% of the radiolabeled DL-DOPA was biotransformed within 10 minutes, reaching peak dopamine levels 20 minutes after administration. …Approximately 0.1% of the dose was present in the brain as (14)Cl-DOPA or (14)C-Dopamine. Levodopa (DL-DOPA)
Over 95% of levodopa was decarboxylated in the periphery by widely distributed extracerebral aromatic L-amino acid decarboxylases. …Almost no unchanged drug entered the cerebral circulation, and perhaps less than 1% penetrated into the central nervous system.
Most was converted to dopamine…Dopamine metabolites were rapidly excreted in the urine, and approximately 80% of the radiolabeled dose was recovered within 24 hours. …These metabolites, 3,4-dihydroxyphenylacetic acid and 3-methoxy-4-hydroxyphenylacetic acid, as well as small amounts of levodopa and dopamine, were also present in the cerebrospinal fluid. For more complete data on the absorption, distribution, and excretion of levodopa (11 types), please visit the HSDB record page.

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Metabolism/Metabolites
L-dopa can be converted to dopamine by aromatic L-amino acid decarboxylases, or to 3-O-methyldopa by catechol-O-methyltransferase O-methylation. 3-O-methyldopa cannot be metabolized to dopamine. After conversion to dopamine, levodopa is converted to sulfated or glucuronidated metabolites, adrenaline E, or homovanillic acid through various metabolic processes. The major metabolites are 3,4-dihydroxyphenylacetic acid (13-47%) and homovanillic acid (23-39%).
Most of it is converted to dopamine…the biotransformation of dopamine is rapid…excretion products are 3,4-dihydroxyphenylacetic acid…and 3-methoxy-4-hydroxyphenylacetic acid…some biochemical evidence suggests that levodopa metabolism is accelerated during long-term treatment, possibly due to enzyme induction.
Over 95%...is decarboxylated by aromatic L-amino acid decarboxylases. A small amount of levodopa is methylated to 3-O-methyldopa...most is converted to dopamine, of which a small amount is further metabolized to norepinephrine and epinephrine.
It is estimated that about three-quarters of dietary methionine is used to metabolize high doses of therapeutic levodopa.
L-DOPA is produced in mammals from L-tyrosine as an intermediate metabolite in the enzymatic synthesis of catecholamines.
After oral administration of levodopa, 95% of the drug is decarboxylated to dopamine by L-aromatic amino acid decarboxylases (AAAD) before reaching the systemic nervous system. Levodopa is mainly distributed in the stomach, intestinal lumen, kidneys, and liver. In addition, levodopa may also be methoxylated by the hepatic catechol-O-methyltransferase (COMT) system to 3-O-methyldopa (3-OMD), which cannot be converted to central dopamine.
Half-life: 50 to 90 minutes

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Biological half-life
The half-life of orally inhaled levodopa is 2.3 hours. The half-life of orally administered levodopa is 50 minutes, but when used in combination with a peripheral dopa decarboxylase inhibitor, the half-life can be extended to 1.5 hours.
Plasma half-life is shorter (1-3 hours).

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Absorption: Oral bioavailability in humans (when used alone) is 30-40%; when used in combination with carbidopa (a peripheral dopa decarboxylase inhibitor), its concentration can be increased to 70-80%. Peak plasma concentration (Cmax) is reached 1-2 hours after oral administration (100 mg dose: Cmax = 1.2 μg/mL) [5]
- Distribution: The volume of distribution (Vd) in the human body is 0.8-1.2 L/kg; it crosses the blood-brain barrier (BBB) via the large neutral amino acid transporter (LAT1), and the brain/plasma concentration ratio is 0.1-0.2 [5]
- Metabolism: It is rapidly metabolized to dopamine by dopa decarboxylase (peripheral and central); it can also be metabolized to 3-O-methyldopa (inactive) by catechol-O-methyltransferase (COMT) [5]
- Excretion: 80% of the metabolites are excreted in urine and 10% in feces. The elimination half-life (t1/2) of levodopa in the human body (when used alone) is 1-2 hours, which can be extended to 2-3 hours when used in combination with carbidopa [5]
- Plasma protein binding rate: The plasma protein binding rate of levodopa (L-DOPA) in human plasma is 10-15% [5]

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
Limited data suggest that levodopa is rarely excreted into breast milk, and sustained-release formulations may result in less drug transfer to the infant from breast milk compared to immediate-release formulations. Multiple studies have shown that levodopa can lower serum prolactin levels during lactation. For mothers who have established lactation, prolactin levels may not affect their ability to breastfeed. Although some mothers with Parkinson's disease have been able to successfully breastfeed without significant adverse effects while using relatively low doses of levodopa and carbidopa, the long-term effects of levodopa use on breastfeeding have not been fully assessed. ◉ Effects on Breastfed Infants
A mother with Parkinson's disease took 200 mg of sustained-release levodopa and 50 mg of carbidopa four times daily. She successfully breastfed her infant, who developed normally at age 2.
A 37-year-old Israeli woman with Parkinson's disease became pregnant while receiving continuous infusions of 20 mg/mL levodopa and 5 mg/mL carbidopa gel. She breastfed her infant for 3 months during treatment, but the extent of breastfeeding and the dosage of the gel were not specified in the paper. The infant's psychomotor development was considered normal at 10 months of age.
◉ Effects on Lactation and Breast Milk
Levodopa can lower serum prolactin levels in normal women and patients with hyperprolactinemia, and can suppress abnormal lactation in patients with galactorrhea, although not always. For mothers who have established lactation, their prolactin levels may not affect their ability to breastfeed.
A mother with Parkinson's disease took 200 mg of sustained-release levodopa and 50 mg of carbidopa four times daily. She successfully breastfed her infant.
On the 3rd day postpartum, five women took 500 mg of levodopa or 5 mg of bromocriptine orally, followed by 10 mg of metoclopramide three hours later. Bromocriptine has a stronger inhibitory effect on basal serum prolactin than levodopa. In the following 3 hours, patients taking levodopa experienced elevated serum prolactin levels after taking metoclopramide, while this was not observed in patients taking bromocriptine. Six postpartum women, 2 to 4 days old but not breastfeeding, were given 500 mg of levodopa orally on day 1 and 100 mg of levodopa plus 35 mg of carbidopa orally on day 2. Both regimens suppressed basal serum prolactin levels. However, levodopa alone reduced prolactin levels by 78%, while the lower-dose combination only reduced them by 51%. The maximum effect of both regimens occurred approximately 2 hours after administration. Seven postpartum women who breastfed approximately 7 times daily during the first week of postpartum were given 500 mg of levodopa orally, and their serum prolactin response was investigated. On day 2, they began taking 50 mg of carbidopa orally every 6 hours for 2 days. On the third day, they received a single oral dose of 50 mg carbidopa and 125 mg levodopa. Baseline serum prolactin levels decreased 30 minutes after levodopa administration and 45 minutes after the combined administration. The largest decrease in drug concentration was observed at 120 minutes post-administration, with a 62% decrease when levodopa was used alone and a 48% decrease when used in combination, but the difference between the two treatment regimens was not statistically significant. A 37-year-old Israeli woman with Parkinson's disease became pregnant while receiving continuous infusion of 20 mg/mL levodopa and 5 mg/mL carbidopa gel. She breastfed her infant for 3 months during the medication period, but the extent of breastfeeding and the gel dosage were not specified in the paper. Protein binding: The binding of levodopa to plasma proteins was negligible.

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Acute toxicity: The oral LD50 in rats was 1890 mg/kg, and the oral LD50 in mice was 1780 mg/kg [1]
- Chronic toxicity: After 6 months of oral administration of levodopa (L-DOPA) (200 mg/kg/day) to rats, increased motor activity and mild intestinal hyperplasia were observed, with no obvious hepatotoxicity or nephrotoxicity [1]
- Clinical side effects: After long-term use (>5 years), 50-60% of patients experienced motor complications (motor disorders, decreased efficacy); 30-40% of patients experienced gastrointestinal symptoms (nausea, vomiting, diarrhea) (carbidopa can alleviate these symptoms); 10-15% of patients experienced mental symptoms (hallucinations, delusions) [5]
- Drug interactions: Co-administration with carbidopa/benserazide (a peripheral dopa decarboxylase inhibitor) reduces peripheral metabolism and increases side effects; COMT inhibitors (e.g., entacapone) prolong the half-life; MAO inhibitors (e.g., phenelzine) increase the risk of hypertensive crisis [5]

[1]. Neuroreport . 1993 Apr;4(4):438-40.

[2]. J Antimicrob Chemother . 2004 Jun;53(6):1086-9.

[3]. Proc Natl Acad Sci U S A, 1997, 94(7), 3363-3367.

[4]. Eur J Neurosci . 2003 Sep;18(6):1607-14.

[5]. Ann Neurol . 1998 May;43(5):561-75.

Levodopa may cause developmental toxicity depending on state or federal labeling requirements. Levodopa is the optically active form of dopamine in the L-configuration. It is used to treat rigidity, tremor, spasticity, and poor muscle control caused by Parkinson's disease. It has multiple functions, including as a prodrug, hapten, neurotoxin, anti-Parkinson's drug, dopaminergic drug, anti-movement disorder drug, allelochemical, plant growth inhibitor, human metabolite, mouse metabolite, and plant metabolite. It is dopamine, an L-tyrosine derivative, and a non-protein L-α-amino acid. It is the conjugate acid of L-dopa (1-). It is the enantiomer of D-dopa. It is the zwitterion tautomer of levodopa. Levodopa is a prodrug of dopamine and is used to treat patients with Parkinson's disease because of its ability to cross the blood-brain barrier. Levodopa can be metabolized into dopamine on both sides of the blood-brain barrier, and therefore is often used in combination with dopa decarboxylase inhibitors (such as carbidopa) to prevent it from being metabolized before crossing the blood-brain barrier. Once it crosses the blood-brain barrier, levodopa is metabolized into dopamine, replenishing the low levels of dopamine in the body and thus treating the symptoms of Parkinson's disease. The first drug approved by the U.S. Food and Drug Administration (FDA) was a combination of levodopa and carbidopa called Sinemet, approved on May 2, 1975. 3,4-Dihydroxy-L-phenylalanine is a metabolite found or produced in Escherichia coli (K12 strain, MG1655 strain). Levodopa is an aromatic amino acid. Levodopa has been reported to exist in edamame (Mucuna macrocarpa), Amanita muscaria, and other organisms with relevant data. Levodopa is an amino acid precursor of dopamine and possesses anti-Parkinson's disease properties. Levodopa is a prodrug that is converted to dopamine by dopa decarboxylase and can cross the blood-brain barrier. In the brain, levodopa is decarboxylated to dopamine, stimulating dopaminergic receptors and thus compensating for the deficiency of endogenous dopamine in Parkinson's disease. To ensure adequate levodopa concentrations in the central nervous system, it is usually used in combination with carbidopa. Carbidopa is a decarboxylase inhibitor that cannot cross the blood-brain barrier, thereby reducing the decarboxylation and inactivation of levodopa in peripheral tissues and increasing dopamine delivery to the central nervous system. Levodopa is used to treat Parkinson's disease and dopa-responsive dystonia, usually in combination with drugs that inhibit its extracentral conversion to dopamine. Conversion in peripheral tissues may be a mechanism by which levodopa causes adverse reactions. Clinically, the common practice is to use a combination of peripheral dopa decarboxylase inhibitors (such as carbidopa or benserazide) and catechol-O-methyltransferase (COMT) inhibitors to inhibit dopamine synthesis in peripheral tissues. Levodopa is the natural form of dihydroxyphenylalanine and a direct precursor to dopamine. Unlike dopamine itself, levodopa can be taken orally and crosses the blood-brain barrier. It is rapidly absorbed by dopaminergic neurons and converted into dopamine. Levodopa is used to treat Parkinson's disease, usually in combination with drugs that inhibit its extracentral conversion into dopamine. [PubChem] Pyridoxal phosphate (vitamin B6) is a cofactor required for this decarboxylation reaction and is usually used in combination with levodopa in the form of pyridoxine. Dihydroxyphenylalanine is a naturally occurring dopamine precursor. Unlike dopamine itself, it can be taken orally and cross the blood-brain barrier. It is rapidly absorbed by dopaminergic neurons and converted into dopamine. It is used to treat Parkinson's disease, usually in combination with drugs that inhibit its extra-central conversion into dopamine. See also: Levodopa (active ingredient); Carbidopa; Levodopa (ingredient); Carbidopa; Entacapone; Levodopa (ingredient)... See more...

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Drug Indications
Levodopa is formulated alone as an oral inhalation powder for intermittent "off-period" treatment in patients with Parkinson's disease receiving carbidopa and levodopa. The most common formulation of levodopa is an oral tablet containing a peripheral dopa decarboxylase inhibitor, used to treat Parkinson's disease, post-encephalitis Parkinson's syndrome, and symptomatic Parkinson's syndrome following carbon monoxide or manganese poisoning.
FDA Label
Inbrija is indicated for the intermittent treatment of paroxysmal motor fluctuations (OFF periods) in adult patients with Parkinson's disease (PD) who are receiving levodopa/dopa decarboxylase inhibitor therapy.
Treatment of Parkinson's Disease

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Mechanism of Action
Levodopa crosses the blood-brain barrier via multiple pathways, decarboxylating to dopamine. Because endogenous dopamine concentrations are low, it cannot exert its effect; therefore, exogenous dopamine supplementation is required, as exogenous dopamine can stimulate dopamine receptors.
The most widely accepted theory is that levodopa can increase dopamine levels, thereby activating dopamine receptors in the extrapyramidal system of the brain (mainly located in the caudate nucleus and substantia nigra).
Existing data suggest that the major effect observed after exogenous levodopa administration is not due to levodopa's direct action on dopamine receptors or the release of dopamine from the striatum, but rather due to the conversion of levodopa to dopamine at serotonergic nerve endings and possibly some striatal cells.
The effects of levodopa on human and mouse melanoma cells were investigated. A characteristic inhibition of thymidine incorporation was observed when exponentially growing cells were exposed to levodopa.
In rats, all dopaminergic agonists resulted in a decrease in serum prolactin levels.
Levodopa (L-DOPA) is a precursor to dopamine, a central nervous system (CNS) neurotransmitter with neuroprotective and antibacterial activities [1,2,3,4,5]. Its core mechanisms include: converting dopamine via dopa decarboxylase to replenish the depleted dopamine in Parkinson's disease patients; protecting dopaminergic neurons from excitotoxic/oxidative stress damage; and inhibiting the growth of Mycobacterium tuberculosis [1,4,5]. Indications include Parkinson's disease (first-line treatment). Used to treat motor symptoms (tremor, rigidity, bradykinesia) and dopa-responsive dystonia [5]
Peripheral metabolism limits its penetration into the blood-brain barrier and causes side effects, so it is almost always used in combination with peripheral dopa decarboxylase inhibitors (carbidopa/benserazide) [5]
Short half-life, requiring multiple daily doses (3-4 times/day) or the use of controlled-release formulations to maintain stable plasma concentrations [5]
It has antibacterial activity against Mycobacterium tuberculosis, suggesting it may be used as an adjunct to the treatment of tuberculosis (clinical validation required) [2]
Long-term use is associated with motor complications, requiring dose adjustment or combination with other Parkinson's disease drugs (e.g., dopamine agonists) [5]

C9H11NO4

197.19

197.068

C, 54.82; H, 5.62; N, 7.10; O, 32.46

59-92-7

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

6047

White to off-white solid powder

1.5±0.1 g/cm3

448.4±45.0 °C at 760 mmHg

276-278 °C(lit.)

225.0±28.7 °C

0.0±1.1 mmHg at 25°C

1.655

-0.22

4

5

3

14

209

1

O([H])C1=C(C([H])=C([H])C(=C1[H])C([H])([H])[C@@]([H])(C(=O)O[H])N([H])[H])O[H]

WTDRDQBEARUVNC-LURJTMIESA-N

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

(2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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).

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 (Please use freshly prepared in vivo formulations for optimal results.)