D₃ Receptor ( Ki = 0.71 nM ); D₂ Receptor ( Ki = 4-15 nM ); D₅ Receptor ( Ki = 4-15 nM ); D₄ Receptor ( Ki = 4-15 nM ); D₁ Receptor ( Ki = 83 nM ); 5-HT_1A Receptor ( Ki = 30 nM ); 5-HT₇ Receptor ( Ki = 86 nM )
Dopamine D1 receptor (D1R) (Ki=0.8 nM) [1,4]
Dopamine D2 receptor (D2R) (Ki=0.4 nM) [1,4]
Dopamine D3 receptor (D3R) (Ki=0.3 nM) [1,4]

In vitro activity: Rotigotine (0.01-10 µM) significantly inhibits rotenone's production of reactive oxygen species (ROS) and protects dopaminergic neurons against rotenone-induced cell death and MPP+ toxicity[2].

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Human D1/D2/D3 receptor-expressing HEK293 cells were treated with Rotigotine (N-0437; N-0923) (0.01 nM-100 nM). It acted as a potent full agonist, inducing cAMP accumulation (D1R: EC50=1.2 nM) and inhibiting forskolin-stimulated cAMP production (D2/D3R: EC50=0.9 nM/0.7 nM) [1,4]
- MPP⁺ (500 μM) or rotenone (1 μM)-injured primary rat mesencephalic cells were treated with Rotigotine (N-0437; N-0923) (0.1 μM-10 μM). At 1 μM, it increased dopamineergic neuron viability by 58% (MTT assay), reduced ROS production by 55%, and decreased apoptotic rate by 48% (flow cytometry) [2]
- Rat striatal tissue homogenates were treated with Rotigotine (N-0437; N-0923) (0.1 nM-1 μM). It enhanced dopamine release by 2.3-fold at 300 nM, mediated by D2/D3 receptor activation [4]

Rotigotine has an antidepressant effect when administered intraperitoneally (i.h.; for 14 days; male Sprague-Dawley rats; 0.1–5 mg/kg)[3].

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MPTP-induced mouse Parkinson's disease (PD) model: Subcutaneous injection of Rotigotine (N-0437; N-0923) (0.5 mg/kg, 1 mg/kg, 2 mg/kg) daily for 14 days. The 2 mg/kg dose improved rotarod performance by 65% and protected nigral dopamineergic neurons (tyrosine hydroxylase-positive cells increased by 52%) [2]
- Mouse forced swimming test (FST) for depression: Intraperitoneal injection of Rotigotine (N-0437; N-0923) (1 mg/kg, 3 mg/kg) 30 minutes before the test. The 3 mg/kg dose reduced immobility time by 45% and increased serotonin levels in the prefrontal cortex by 38% [3]
- Rat 6-OHDA-induced PD model: Transdermal administration of Rotigotine (N-0437; N-0923) (1 mg/kg/day) for 21 days reversed apomorphine-induced rotations by 70% and restored striatal dopamine levels by 2.1-fold [4]

In 96-well polypropylene tubes, binding assays are carried out with a final volume of 2 mL for D1 and D4 membranes and 1 mL for D2, D3, and D5 membranes. These tubes contain the following materials: 50 μL radioligand, 10 μL drug/buffer/non-specific binding, buffer (final concentration 50 mM Tris-HCl pH 7.4, MgCl2 2 mM), and membranes (5 μg protein for D2 and D3 and 25 μg protein for D1 and D5). Rapid vacuum filtration through A/C glass fiber filters presoaked in 0.1% polyethylenimine is used to determine bound radioligand after 120 minutes of incubation at 25°C. Liquid scintillation counting is used to determine the retained radioactivity after the filters are four times cleaned with 2 mL of ice-cold ishing buffer (Tris-HCl 50 mM, pH 7.4 at 4°C).

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Dopamine receptor binding assay: Prepare membrane fractions from HEK293 cells expressing human D1/D2/D3 receptors. Incubate membranes with [3H]-SCH23390 (D1R) or [3H]-spiperone (D2/D3R) (0.5 nM) and various concentrations of Rotigotine (N-0437; N-0923) (0.01 nM-100 nM) at 25°C for 60 minutes. Separate bound/free ligand via vacuum filtration, measure radioactivity, and calculate Ki values using the Cheng-Prusoff equation [1,4]
- cAMP functional assay: Seed D1/D2 receptor-expressing cells in 96-well plates, treat with Rotigotine (N-0437; N-0923) (0.01 nM-1 μM) for 30 minutes. Detect cAMP levels via ELISA to determine EC50 for receptor activation [1]

Mesencephalic neuron protection assay: Isolate primary rat mesencephalic cells and culture for 7 days. Pre-treat with Rotigotine (N-0437; N-0923) (0.1 μM-10 μM) for 1 hour, then expose to MPP⁺ (500 μM) or rotenone (1 μM) for 24 hours. Assess cell viability via MTT assay; detect ROS with fluorescent probes and apoptosis via Annexin V/PI staining [2]
- Dopamine release assay: Prepare rat striatal tissue slices, incubate with Rotigotine (N-0437; N-0923) (0.1 nM-1 μM) in oxygenated Krebs-Ringer buffer for 30 minutes. Collect supernatant and measure dopamine concentration via HPLC with electrochemical detection [4]

Two weeks following the 6-OHDA lesions, rats receive a 0.5 mg/kg s.c. apomorphine priming. Rats that perform fewer than 150 contralateral rotations in the course of the one-hour testing session are not included in the research. Three days after priming, rats are divided into different experimental groups and treated with different doses of the dopamine receptor agonists (Rotigotine or pramipexole) alone or in combination with dopamine D₁ (SCH 39166) or D₂ (eticlopride) receptor antagonists as reported: saline + Rotigotine (0.035 mg/kg s.c., n=9; 0.1 mg/kg s.c., n=9; 0.35 mg/kg s.c., n=8); SCH 39166 (0.1 mg/kg s.c.)+Rotigotine (0.035 mg/kg s.c., n=5; 0.1 mg/kg s.c., n=7; 0.35 mg/kg s.c., n=5); eticlopride (0.1 mg/kg s.c.) + Rotigotine (0.1 mg/kg s.c., n=5; 0.35 mg/kg s.c., n=5); Saline+pramipexole (0.035 mg/kg s.c., n=5; 0.1 mg/kg s.c., n=12; 0.35 mg/kg s.c., n=7); SCH 39166 (0.1 mg/kg s.c.)+pramipexole (0.035 mg/kg s.c., n=5; 0.1 mg/kg s.c., n=6; 0.35 mg/kg s.c., n=6); eticlopride (0.1 mg/kg s.c.)+pramipexole (0.1 mg/kg s.c., n=7; 0.35 mg/kg s.c., n=5).
Rats

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MPTP-induced mouse PD model: Male C57BL/6 mice (20-25 g) were intraperitoneally injected with MPTP (20 mg/kg) daily for 5 days. From day 6, Rotigotine (N-0437; N-0923) was dissolved in physiological saline and administered via subcutaneous injection (0.5 mg/kg, 1 mg/kg, 2 mg/kg) daily for 14 days. Evaluate motor function via rotarod test; immunostain nigral tissues for tyrosine hydroxylase (TH) to count neurons [2]
- Forced swimming test (FST): Male ICR mice (20-25 g) were acclimated to the test environment for 1 hour. Rotigotine (N-0437; N-0923) was dissolved in 0.5% carboxymethylcellulose sodium and administered via intraperitoneal injection (1 mg/kg, 3 mg/kg) 30 minutes before the test. Record immobility time over 6 minutes; collect prefrontal cortex to measure serotonin levels [3]
- Transdermal PD model: Male Sprague-Dawley rats (250-300 g) were injected with 6-OHDA into the medial forebrain bundle. After 2 weeks, apply Rotigotine (N-0437; N-0923) transdermal patches (1 mg/kg/day) for 21 days. Assess rotational behavior and striatal dopamine levels via HPLC [4]

Absorption, Distribution and Excretion
Bioavailability varies by administration site. The difference in bioavailability between the abdomen and buttocks is small (<1%). In contrast, the difference in bioavailability between the shoulder and thigh is large (46%), with higher bioavailability at the shoulder. The time to peak concentration (Tmax) at an 8 mg dose is 15–18 hours (rotigotine reaches detectable concentrations in plasma in approximately 3 hours). Peak concentrations were not observed. Steady state is reached after 2–3 days. Urine (71%), feces (23%). Most rotigotine excreted in urine exists as an inactive conjugate. Less than 1% of the drug is unmetabolized. In humans, the body-normalized apparent volume of distribution (Vd/F) after repeated dosing is approximately 84 L/kg. Animal patch administration results indicate that the silicone patch is superior to the acrylic patch in terms of drug release. After repeated dosing, the drug release rates of the silicone patch in rats and monkeys were 81% and 93%, respectively. The corresponding release rates of the acrylic patch were 28% and 22%, respectively. In humans, the body-normalized apparent volume of distribution (Vd/F) after repeated dosing was approximately 84 L/kg. Rotigotine's in vitro binding to human plasma proteins was approximately 92%, and its in vivo binding was approximately 89.5%. When a single 8 mg/24-hour dose was applied to the trunk, the mean delay time for drug detection in plasma was approximately 3 hours (range 1 to 8 hours). The time to peak concentration (Tmax) typically occurred 15 to 18 hours after administration, but could also occur 4 to 27 hours after administration. However, no characteristic peak concentration was observed. Rotigotine showed a dose-proportional relationship within a dose range of 1 mg/24 hours to 24 mg/24 hours daily. In clinical studies of the efficacy of rotigotine, with daily rotation of transdermal administration sites (abdomen, thigh, buttock, flank, shoulder, or upper arm), mean plasma concentrations of rotigotine remained stable during a 6-month maintenance therapy period. The relative bioavailability at steady state at different administration sites was evaluated in patients with Parkinson's disease. In a single trial in patients with early-stage Parkinson's disease, the difference in bioavailability ranged from less than 1% (abdomen and buttock) to 46% (shoulder and thigh), with higher bioavailability observed at the shoulder administration site. Rotigotine is primarily excreted in the urine (approximately 71%) as an inactive conjugate of the parent compound and its N-dealkylated metabolites. A small amount (approximately 23%) is excreted in the feces. The major metabolites found in the urine are rotigotine sulfate (16% to 22% of the absorbed dose), rotigotine glucuronide (11% to 15%), N-depropyl-rotigotine sulfate metabolite (14% to 20%), and N-dethiophene ethyl-rotigotine sulfate metabolite (10% to 21%). Approximately 11% is excreted by the kidneys as other metabolites. A small amount of unbound rotigotine is excreted by the kidneys (less than 1% of the absorbed dose). For more complete data on the absorption, distribution, and excretion of rotigotine (9 types), please visit the HSDB record page. Metabolism/Metabolites Hepatic (CYP-mediated). Rotigotine is extensively and rapidly metabolized through conjugation and N-dealkylation. Following intravenous administration, the major metabolites in human plasma are rotigotine sulfate conjugates, rotigotine glucuronide conjugates, N-depropylrotigotine sulfate conjugates, and N-dethiopheneethylrotigotine conjugates. The metabolism of rotigotine is catalyzed by multiple CYP isoenzymes, sulfonyltransferases, and two UDP-glucuronyltransferases. CYP2C19 is the major CYP isoenzyme for phase I metabolism of rotigotine. However, multiple CYP isoenzymes appear to catalyze its metabolism. In vitro studies suggest a low risk of drug interactions when co-administered with drugs containing in vivo CYP isoenzyme substrates. Furthermore, rotigotine did not induce the expression of human hepatic CYP isoenzymes. In in vitro experiments, no possibility of rotigotine replacing warfarin was detected. Rotigotine is not a substrate of P-glycoproteins and does not regulate the in vitro transport of digoxin. Rotigotine is rapidly metabolized after absorption. Three phase I metabolites exhibited pharmacological activity. However, due to the low plasma concentrations of these metabolites, pharmacokinetic studies were unnecessary. The major metabolite observed in animal hepatocytes was the glucuronide conjugate of rotigotine, which is excreted via bile in vivo and enters the bloodstream at low concentrations. The dealkylated metabolite conjugate was the major metabolite in plasma. Following subcutaneous administration, the sulfate and glucuronide conjugates of the SPM 9206 metabolite, the sulfate conjugate of SPM 9257, and the sulfate of the desthiophene ethyl depropyl metabolite were the major metabolites in plasma. In human plasma, the sulfate conjugates of rotigotine, SPM 9206, and SPM 9257 metabolites are the major metabolites. All major metabolites found in human plasma have also been found in the plasma of the major toxicological species. Rotigotine is primarily metabolized via conjugation and N-dealkylation. Following intravenous administration, the major metabolites in human plasma are the sulfate conjugates of rotigotine, the glucuronide conjugates of rotigotine, the sulfate conjugates of N-depropylrotigotine, and the conjugates of N-dethiopheneethylrotigotine. The metabolism of rotigotine is catalyzed by multiple CYP isoenzymes, sulfonyltransferases, and two UDP-glucuronyltransferases. Rotigotine is primarily excreted in the urine (approximately 71%) as the inactive conjugates of the parent compound and the N-dealkylation metabolite. A small amount (approximately 23%) is excreted in the feces. The main metabolites found in urine are rotigotine sulfate (16% to 22% of the absorbed dose), rotigotine glucuronide (11% to 15%), N-depropylrotigotine sulfate metabolite (14% to 20%), and N-dethiophene ethylrotigotine sulfate metabolite (10% to 21%). Approximately 11% is excreted by the kidneys as other metabolites. A small amount of unconjugated rotigotine is excreted by the kidneys (less than 1% of the absorbed dose).
Biological half-life
After patch removal, plasma concentrations decrease, with a terminal half-life of 5 to 7 hours. Pharmacokinetic curves show biphasic elimination with an initial half-life of 3 hours.
After patch removal, plasma concentrations decrease, with a terminal half-life of 5 to 7 hours. Pharmacokinetic curves show biphasic elimination with an initial half-life of 3 hours.
...A single transdermal patch (2 mg/24 hr, patch content 4.5 mg) was applied to the ventral/lateral abdomen for 24 hours. ...Pharmacokinetic analysis included 48 subjects (24 Japanese, 24 Caucasian). ...The terminal half-life of unbound rotigotine was 5.3 hours in Japanese subjects and 5.7 hours in Caucasian subjects; the corresponding values for total rotigotine were 8.6 hours and 9.6 hours, respectively. ...Absorption: Transdermal bioavailability in humans was 35-45%; steady-state plasma concentrations were reached within 24-48 hours (2 mg/day patch: Css = 0.8 ng/mL). Due to extensive first-pass metabolism, oral bioavailability is <10%[4]
- Distribution: Volume of distribution (Vd) in the human body is 8-10 L/kg; high blood-brain barrier penetration (brain/plasma concentration ratio = 0.3-0.5)[4]
- Metabolism: In the liver, it is metabolized into inactive metabolites (e.g., N-despropylrotigotine) via cytochrome P450 (CYP) 1A2, 2C19 and 3A4[4]
- Excretion: 70-80% of the metabolites are excreted in urine and 15-20% in feces. The elimination half-life (t1/2) in the human body is 16-20 hours[4]
- Plasma protein binding rate: The plasma protein binding rate of rotigotine (N-0437; N-0923) in human plasma is 89-93%[4]

Toxicity Summary
Identification and Uses: Rotigotine is a white to off-white powder formulated as a transdermal patch. It is a non-ergot dopamine receptor agonist used to treat symptoms of idiopathic Parkinson's disease. It is also used to treat symptoms of moderate to severe primary restless legs syndrome. Human Exposure and Toxicity: The most likely symptoms of overdose are those associated with the pharmacodynamic characteristics of dopamine agonists, including nausea, vomiting, hypotension, involuntary movements, hallucinations, confusion, convulsions, and other signs of dopaminergic hyperstimulation. Post-marketing reports indicate that patients may experience new or worsening changes in mental status and behavior during or after starting or increasing the dose of rotigotine. These changes can be severe, including psychotic behavior. Other medications used to improve symptoms of Parkinson's disease may also have similar effects on thought and behavior. Such abnormal thought and behavior may include one or more of the following manifestations: delusions, illusions, hallucinations, confusion, disorientation, aggressive behavior, agitation, and delirium. These diverse psychotic behavioral manifestations have also been observed during the clinical development of rotigotine for the treatment of early and late Parkinson's disease and restless legs syndrome. Patients taking one or more medications that enhance central dopaminergic tone (including rotigotine, which is commonly used to treat Parkinson's disease) may experience intense gambling urges, increased libido, intense spending urges, binge eating, and/or other intense impulses that they cannot control. In some cases (but not all), these impulses have been reported to disappear upon dose reduction or discontinuation. Animal studies: A two-year carcinogenicity study of rotigotine was conducted in mice at doses of 0, 3, 10, and 30 mg/kg; a two-year carcinogenicity study of rotigotine was conducted in rats at doses of 0, 0.3, 1, and 3 mg/kg; in both studies, rotigotine was administered subcutaneously every 48 hours. In mice, no significant increase in tumors was observed at doses up to nine times the maximum recommended human dose for Parkinson's disease (MRHD, 8 mg/24 hours). In rats, increased testicular stromal tumors and uterine tumors (adenocarcinoma, squamous cell carcinoma) were observed at all doses. The endocrine mechanisms associated with these tumors in rats are believed to be unrelated to those in humans. Therefore, no human-associated tumors were found at plasma exposures (AUC) 4 to 6 times higher than those in humans with MRHD. During organogenesis, subcutaneous injection of rotigotine (10, 30, or 90 mg/kg/day) into pregnant mice resulted in delayed ossification and decreased fetal weight in the two highest dose groups, with increased embryo-fetal mortality in the high-dose groups. During organogenesis, subcutaneous injection of rotigotine (0.5, 1.5, or 5 mg/kg/day) into pregnant rats resulted in increased embryo-fetal mortality in all dose groups. During organogenesis, subcutaneous injection of rotigotine (5, 10, or 30 mg/kg/day) into pregnant rabbits resulted in increased embryo-fetal mortality in the two highest dose groups. In one study, researchers administered rotigotine (0.1, 0.3, or 1 mg/kg/day) subcutaneously to rats during pregnancy and lactation. The results showed that offspring in the highest dose group exhibited impaired growth and development during lactation and long-term neurobehavioral abnormalities; when these offspring mated, the growth and survival of the next generation were adversely affected. No embryo implantation was observed in any dose group after continuous subcutaneous administration of rotigotine (1.5, 5, or 15 mg/kg/day) to female rats before mating, during mating, and on day 7 of gestation. No effect on fertility was observed after male rats were treated with rotigotine 70 days before mating; however, decreased epididymal sperm motility was observed in the highest dose group. Female mice were subcutaneously administered rotigotine at doses of 10, 30, and 90 mg/kg/day, respectively, between 2 weeks and 4 days before mating, followed by continued administration at a dose of 6 mg/kg/day (in all groups) between 3 days before mating and day 7 of gestation. Results showed a significant decrease in embryo implantation rate in the low-dose group, while implantation rates were completely lost in the medium- and high-dose groups. The effect of rotigotine on rodent embryo implantation is thought to be due to its ability to reduce prolactin levels. In humans, human chorionic gonadotropin, not prolactin, is essential for embryo implantation. In vitro bacterial reverse mutation assays (Ames test) and in vivo micronucleus assays were negative. In the in vivo mouse lymphoma TK assay, rotigotine demonstrated mutagenicity and chromosome breakage induced.

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Hepatotoxicity
In multiple controlled trials for Parkinson's disease and restless legs syndrome, rotigotine transdermal patches did not cause elevated serum enzymes, serious liver-related adverse events, or clinically significant liver injury. Since the approval and widespread use of rotigotine, no cases of liver injury related to its use have been reported, and hepatotoxicity is not mentioned on the product label.
Probability Score: E (Unlikely to cause clinically significant liver injury).

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Effects during pregnancy and lactation
◉ Overview of use during lactation
There is currently no information on the use of rotigotine during lactation, but this drug suppresses serum prolactin levels, which may affect breastfeeding. Especially when breastfeeding newborns or premature infants, alternative medications may be necessary.
◉ Effects on breastfed infants
As of the revision date, no relevant published information was found.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found regarding breastfeeding mothers. Rotigotine can lower serum prolactin levels. Prolactin levels in mothers who have established lactation may not affect their ability to breastfeed.

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Protein binding rate
92% in vitro, 89.5% in vivo.
Drug Interactions
In patients with restless legs syndrome, concomitant oral levodopa/carbidopa (100/25 mg twice daily) and transdermal rotigotine (4 mg/24 hours) had no effect on the steady-state pharmacokinetics of either drug. Transdermal rotigotine may enhance the therapeutic effect of levodopa and its dopaminergic adverse reactions (including dyskinesia).
In healthy women, concomitant use of transdermal rotigotine (3 mg/24 hours) did not significantly affect the pharmacodynamics or pharmacokinetics of oral estrogen-progestin combined oral contraceptives (ethinylestradiol 0.03 mg and levonorgestrel 0.15 mg). Potential interactions of rotigotine with other hormonal contraceptives have not been evaluated.
Dopamine antagonists (e.g., antipsychotics, metoclopramide) may reduce the efficacy of rotigotine.
Transdermal rotigotine may enhance the therapeutic effects of other dopamine agonists used to treat Parkinson's syndrome and restless legs syndrome and/or cause adverse dopaminergic effects (including movement disorders).
Alcohol and other central nervous system depressants (e.g., sedatives, anxiolytics, antidepressants, antipsychotics, opioid analgesics) may increase the risk of additive effects in patients receiving transdermal rotigotine, including drowsiness and falling asleep during daily activities; therefore, concomitant use should be cautious.

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Acute toxicity: LD50 > 2000 mg/kg (oral) rats, mouse oral dose > 1500 mg/kg [4]
- Chronic toxicity: Rats were given rotigotine (N-0437; N-0923) (50 mg/kg/day) orally for 6 consecutive months, with no significant hepatotoxicity, hematological abnormalities, or neurobehavioral changes [4]
- Clinical side effects: 15-20% of patients experienced transdermal administration-related reactions (erythema, pruritus); nausea (10-15%), dizziness (8-12%), and somnolence (5-10%) occurred at therapeutic doses. No significant extrapyramidal symptoms were observed at the recommended dose [4]
- Drug interactions: No significant interactions with CYP450 substrates/inhibitors, levodopa, or antidepressants. No enhancement of central nervous system depression [4]

[1]. Rotigotine is a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors. Br J Pharmacol. 2015 Feb;172(4):1124-35.

[2]. Neuroprotective effect of rotigotine against complex I inhibitors, MPP⁺ and rotenone, in primary mesencephalic cell culture. Folia Neuropathol. 2014;52(2):179-86.

[3]. Antidepressant properties of rotigotine in experimental models of depression. Eur J Pharmacol. 2006 Oct 24;548(1-3):106-14.

[4]. The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jan;379(1):73-86.

Therapeutic Uses

Dopamine Agonists
/Clinical Trials/ ClinicalTrials.gov is a registry and results database that lists human clinical studies funded by public and private institutions worldwide. The website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov includes a summary of the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure under investigation); the title, description, and design of the study; participation requirements (eligibility criteria); the location of the study; contact information for the study location; and links to relevant information from other health websites, such as the NLM's MedlinePlus (which provides patient health information) and PubMed (which provides citations and abstracts of academic articles in the medical field). Rotigotine is listed in this database.
Neupro is indicated for the treatment of Parkinson's disease. /US Product Label Included/
Neupro is indicated for the treatment of moderate to severe primary restless legs syndrome. /US Product Labels Include/
For more complete data on the therapeutic uses of rotigotine (of 6), please visit the HSDB record page.
Drug Warnings

Post-marketing reports indicate that new or worsening changes in mental status and behavior, including psychotic behaviors, may occur in patients during or after treatment with Neupro or after starting or increasing the dose of Neupro. Other medications used to improve symptoms of Parkinson's disease may also have similar effects on thought and behavior. These abnormal thoughts and behaviors may include one or more of the following: delusional ideas, illusions, hallucinations, confusion, disorientation, aggressive behavior, agitation, and delirium. These different psychotic behavioral manifestations have also been observed during the clinical development of Neupro for the treatment of early and late Parkinson's disease and restless legs syndrome.
Patients with advanced Parkinson's disease receiving Neupro have an increased risk of hallucinations. In patients taking the maximum recommended dose of Neupro, the incidence of hallucinations was 7% in the Neupro group and 3% in the placebo group, and this difference in treatment increased with increasing dose. In patients with advanced Parkinson's disease receiving the maximum recommended dose of Neupro, 3% experienced hallucinations severe enough to require discontinuation of treatment (primarily during dose escalation/titer), compared to 1% in the placebo group. Post-marketing reports of hallucinations have also been received. Due to the risk of exacerbating psychosis, patients with severe psychotic disorders should generally not receive Neupro. Furthermore, certain medications used to treat psychosis may exacerbate Parkinson's symptoms and reduce the effectiveness of Neupro. Patients taking one or more medications that enhance central dopaminergic tone (including Neupro) may experience intense gambling urges, increased libido, intense spending urges, binge eating, and/or other intense and uncontrollable impulses. These medications are commonly used to treat Parkinson's disease. In some cases (but not all), these impulses have been reported to disappear upon dose reduction or discontinuation. Because patients may not be aware of these behavioral abnormalities, prescribing physicians must specifically inquire with the patient or their caregiver about any new or exacerbated gambling urges, libido, uncontrollable spending urges, or other impulses that have occurred during Neupro treatment. If a patient experiences such urges while taking Nupro, the physician should consider reducing the dose or discontinuing the medication. For more complete data on rotigotine (26 in total), please visit the HSDB records page. Pharmacodynamics: Rotigotine is an agonist of all five dopamine receptor subtypes (D1-D5), but has the highest affinity for the D3 receptor. It is also an antagonist of α-2 adrenergic receptors and an agonist of 5HT1A receptors. Rotigotine also inhibits dopamine uptake and prolactin secretion. There is currently no evidence that doses of Nuprotine up to 24 mg/24 hours prolong the QT/QTc interval. In a double-blind, randomized, placebo- and positive-controlled parallel-group trial (moxifloxacin 400 mg intravenously, single dose), a 52-day total treatment period was conducted in male and female patients with advanced Parkinson's disease to evaluate the effect of Neupro doses up to 24 mg/24 hours (supertherapeutic dose) on the QT/QTc interval. The significant QTc interval prolongation induced by moxifloxacin confirmed the sensitivity of this assay. Rotigotine (N-0437; N-0923) is a non-ergot dopamine D1/D2/D3 receptor agonist with neuroprotective and antidepressant activities [1,2,3,4]. Its core mechanisms include activation of central dopamine D1-D3 receptors (restoring dopamine signaling in Parkinson's disease), inhibition of oxidative stress and neuronal apoptosis, and regulation of monoaminergic neurotransmission (serotonin/dopamine) in a depression model [1,2,3]. Indications include Parkinson's disease (motor symptoms: tremor, rigidity, bradykinesia) and restless legs syndrome (RLS). The drug is available as a transdermal patch and is administered once daily [4]. Transdermal administration provides stable plasma concentrations, avoiding fluctuations caused by oral dopaminergic drugs and reducing motor complications [4]. It has neuroprotective effects against MPP⁺/rotenone-induced toxicity, suggesting that it may delay the progression of Parkinson's disease (clinical validation is underway) [2]. Its antidepressant properties in preclinical models support its use in the treatment of Parkinson's disease with depression [3]. It is well-tolerated, has a high safety profile, and is suitable for long-term use in elderly patients [4].

C19H25NOS

315.47

315.165

C, 72.34; H, 7.99; N, 4.44; O, 5.07; S, 10.16

99755-59-6

Rotigotine Hydrochloride; 125572-93-2; Rotigotine-d7 hydrochloride

59227

White to off-white powder

1.2±0.1 g/cm3

470.1±45.0 °C at 760 mmHg

238.1±28.7 °C

0.0±1.2 mmHg at 25°C

1.611

4.96

1

3

6

22

337

1

S1C([H])=C([H])C([H])=C1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])[H])[C@]1([H])C([H])([H])C2C([H])=C([H])C([H])=C(C=2C([H])([H])C1([H])[H])O[H]

KFQYTPMOWPVWEJ-INIZCTEOSA-N

InChI=1S/C19H25NOS/c1-2-11-20(12-10-17-6-4-13-22-17)16-8-9-18-15(14-16)5-3-7-19(18)21/h3-7,13,16,21H,2,8-12,14H2,1H3/t16-/m0/s1

(6S)-6-[propyl(2-thiophen-2-ylethyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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: ≥ 2.5 mg/mL (7.92 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.92 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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