Tìm theo
Rotigotine
antidyskinetics
Thuốc Gốc
Small Molecule
CAS: 92206-54-7
ATC: N04BC09
CTHH: C19H25NOS
PTK: 315.473
Rotigotine (Neupro) is a non-ergoline dopamine agonist indicated for the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS) in Europe and the United States. It is formulated as a once-daily transdermal patch which provides a slow and constant supply of the drug over the course of 24 hours. Like other dopamine agonists, rotigotine has been shown to possess antidepressant effects and may be useful in the treatment of depression as well. Rotigotine was developed by Aderis Pharmaceuticals. In 1998, Aderis licensed worldwide development and commercialization rights for rotigotine to the German pharmaceutical company Schwarz Pharma (today a subsidiary of the Belgian company UCB S.A.). The drug has been approved by the EMEA for use in Europe in 2006 and is today being sold in several European countries. In 2007, the Neupro patch was approved by the Food and Drug Administration (FDA) as the first transdermal treatment of Parkinson's disease in the United States. However, as of 2008, Schwarz Pharma has recalled all Neupro patches in the United States and some in Europe because of problems with the delivery mechanism. Rotigotine has been authorized as a treatment for RLS since August 2008.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H25NOS
Phân tử khối
315.473
Monoisotopic mass
315.165685117
InChI
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
InChI Key
InChIKey=KFQYTPMOWPVWEJ-UHFFFAOYSA-N
IUPAC Name
6-{propyl[2-(thiophen-2-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-1-ol
Traditional IUPAC Name
rotigotine
SMILES
CCCN(CCC1=CC=CS1)C1CCC2=C(C1)C=CC=C2O
Độ hòa tan
9.04e-03 g/l
logP
4.70
logS
-4.5
pKa (strongest acidic)
10.03
pKa (Strongest Basic)
10.97
PSA
23.47 Å2
Refractivity
94.56 m3·mol-1
Polarizability
37.17 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
2
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : Rotigotine is an agonist at all 5 dopamine receptor subtypes (D1-D5) but binds to the D3 receptor with the highest affinity. It is also an antagonist at α-2-adrenergic receptors and an agonist at the 5HT1A receptors. Rotigotine also inhibits dopamine uptake and prolactin secretion. There is no indication of a QT/QTc prolonging effect of Neupro in doses up to 24 mg/24 hours. The effects of Neupro at doses up to 24 mg/24 hours (supratherapeutic doses) on the QT/QTc interval was evaluated in a double-blind, randomized, placebo- and positive-controlled (moxifloxacin 400 mg IV, single dose) parallel-group trial with an overall treatment period of 52 days in male and female patients with advanced-stage Parkinson's disease. Assay sensitivity was confirmed by significant QTc prolongation by moxifloxacin.
Cơ Chế Tác Dụng : Rotigotine (Neupro) is a non-ergoline dopamine agonist indicated for the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS) in Europe and the United States. It is formulated as a once-daily transdermal patch which provides a slow and constant supply of the drug over the course of 24 hours. Like other dopamine agonists, rotigotine has been shown to possess antidepressant effects and may be useful in the treatment of depression as well. Rotigotine was developed by Aderis Pharmaceuticals. In 1998, Aderis licensed worldwide development and commercialization rights for rotigotine to the German pharmaceutical company Schwarz Pharma (today a subsidiary of the Belgian company UCB S.A.). The drug has been approved by the EMEA for use in Europe in 2006 and is today being sold in several European countries. In 2007, the Neupro patch was approved by the Food and Drug Administration (FDA) as the first transdermal treatment of Parkinson's disease in the United States. However, as of 2008, Schwarz Pharma has recalled all Neupro patches in the United States and some in Europe because of problems with the delivery mechanism. Rotigotine has been authorized as a treatment for RLS since August 2008. Rotigotine, a member of the dopamine agonist class of drugs, is delivered continuously through the skin (transdermal) using a silicone-based patch that is replaced every 24 hours. A dopamine agonist works by activating dopamine receptors in the body, mimicking the effect of the neurotransmitter dopamine. The precise mechanism of action of rotigotine as a treatment for Restless Legs Syndrome is unknown but is thought to be related to its ability to stimulate dopamine
Dược Động Học :
▧ Absorption :
Bioavailability varies depending on the application site. Differences in bioavailability were very small between the abdomen and hip (<1%). In contrast, the shoulder and thigh had a very large different in measured bioavailability (46%), with the shoulder showing the higher value. Tmax, 8 mg dose = 15 - 18 hours (it take approximately 3 hours until rotigotine reaches detectable levels in the plasma). The peak concentration cannot be observered. Steady state is reached in 2-3 days.
▧ Volume of Distribution :
The weight normalized apparent volume of distribution, (Vd/F), in humans is approximately 84 L/kg after repeated dose administration.
▧ Protein binding :
92% in vitro and 89.5% in vivo.
▧ Metabolism :
Hepatic (CYP-mediated). Rotigotine is extensively and rapidly metabolized by conjugation and N-dealkylation. After intravenous dosing the predominant metabolites in human plasma are sulfate conjugates of rotigotine, glucuronide conjugates of rotigotine, sulfate conjugates of the N-despropyl-rotigotine and conjugates of N-desthienylethyl-rotigotine. Multiple CYP isoenzymes, sulfotransferases and two UDP-glucuronosyltransferases catalyze the metabolism of rotigotine.
▧ Route of Elimination :
Urine (71%), Fecal (23%). Most of rotigotine that is excreted in the urine is in the form of inactive conjugates. Unchanged drug made up less <1%.
▧ Half Life :
After removal of the patch, plasma levels decreased with a terminal half-life of 5 to 7 hours. The pharmacokinetic profile showed a biphasic elimination with an initial half-life of 3 hours.
Độc Tính : The most likely symptoms of overdose would be those related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, hypotension, involuntary movements, hallucinations, confusion, convulsions, and other signs of excessive dopaminergic stimulation.
Chỉ Định : For use/treatment in neurologic disorders and parkinson's disease as well as moderate-to-severe primary Restless Legs Syndrome.
Tương Tác Thuốc :
  • Clobazam Concomitant therapy may potentiate adverse CNS effects such as increased sedation or respiratory depression. Monitor therapy closely.
  • Dihydrocodeine Dihydrocodeine may enhance the sedative effect of rotigotine. It is recommended to monitor therapy.
  • Enflurane Risk of sedation may increase with concomitant therapy. Monitor therapy closely.
  • Ephedrine Risk of sedation may decrease with concomitant therapy. Monitor therapy closely.
  • Fentanyl Pharmacodynamic synergism may increase the effects of rotigotine. Monitor therapy closely.
  • Loxapine Pharmacodynamic antagonism may decrease the effects of rotigotine. Consider alternate therapy.
  • Thiothixene Thiothixene may antaonize the effects of the anti-Parkinsonian agent, Rotigotine. Consider alternate therapy or monitor for decreased effects of both agents.
  • Triprolidine The CNS depressants, Triprolidine and Rotigotine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
  • Ziprasidone The atypical antipsychotic, ziprasidone, may antagonize the effect of the dopamine agonist, rotigotine. Consider alternate therapy or monitor for worsening of movement disorder.
  • Zuclopenthixol Antagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and rotigotine, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
Liều Lượng & Cách Dùng : Patch, extended release - Transdermal - 1 mg/24 hr; 2 mg/24 hr; 3 mg/24 hr; 4 mg/24 hr; 6 mg/24 hr; 8 mg/24 hr
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty : UCB, Inc.
    Sản phẩm biệt dược : Neupro
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB05271
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=57537
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=99443232
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D05768
ChemSpider
http://www.chemspider.com/Chemical-Structure.51867.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50054062
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/50474-801-03
PharmGKB
http://www.pharmgkb.org/drug/PA165958352
Wikipedia
http://en.wikipedia.org/wiki/Rotigotine
RxList
http://www.rxlist.com/neupro-drug.htm
Drugs.com
http://www.drugs.com/cons/rotigotine-transdermal.html
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