Human Metabolome Database: Showing metabocard for Rotigotine (HMDB15615)

You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.

Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (9) Show 9 proteins XML

enzymes (9) Show 9 proteins

Record Information

Version

3.6

Creation Date

2012-09-06 15:16:52 UTC

Update Date

2017-03-02 21:34:06 UTC

HMDB ID

HMDB15615

Secondary Accession Numbers

None

Metabolite Identification

Common Name

Rotigotine

Description

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.

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Value	Source
2-(N-N-Propyl-N-2-thienylethylamino)-5-hydroxytetralin	MeSH
N 0437, (R)-Isomer	MeSH
N 0437, Hydrochloride, (S)-isomer	MeSH
Neupro	MeSH
N 0437, Hydrochloride, (R)-isomer	MeSH
Rotigotine CDS	MeSH
N 0437, (+-)-Isomer	MeSH
N 0437, (-)-Isomer	MeSH

Chemical Formula

C₁₉H₂₅NOS

Average Molecular Weight

315.473

Monoisotopic Molecular Weight

315.165685117

IUPAC Name

6-{propyl[2-(thiophen-2-yl)ethyl]amino}-5,6,7,8-tetrahydronaphthalen-1-ol

Traditional Name

rotigotine

CAS Registry Number

92206-54-7

SMILES

CCCN(CCC1=CC=CS1)C1CCC2=C(C1)C=CC=C2O

InChI Identifier

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

KFQYTPMOWPVWEJ-UHFFFAOYSA-N

Chemical Taxonomy

Description

This compound belongs to the class of chemical entities known as tetralins. These are polycyclic aromatic compounds containing a tetralin moiety, which consists of a benzene fused to a cyclohexane.

Kingdom

Super Class

Class

Sub Class

Direct Parent

Alternative Parents

Substituents

Tetralin
1-hydroxy-4-unsubstituted benzenoid
1-hydroxy-2-unsubstituted benzenoid
Aralkylamine
Thiophene
Heteroaromatic compound
Tertiary amine
Tertiary aliphatic amine
Organoheterocyclic compound
Hydrocarbon derivative
Organopnictogen compound
Organic oxygen compound
Organic nitrogen compound
Organooxygen compound
Organonitrogen compound
Amine
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Ontology

Status

Expected but not Quantified

Origin

Drug

Biofunction

Antidyskinetics
Antiparkinson Agents
Dopamine Agonists

Application

Pharmaceutical

Cellular locations

Membrane

Physical Properties

State

Solid

Experimental Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	9.04e-03 g/L	Not Available
LogP	4.70	BIOBYTE STARLIST (2009)

Predicted Properties

Property	Value	Source
Water Solubility	0.009 mg/mL	ALOGPS
logP	5.01	ALOGPS
logP	4.34	ChemAxon
logS	-4.5	ALOGPS
pKa (Strongest Acidic)	10.03	ChemAxon
pKa (Strongest Basic)	10.97	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	23.47 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	94.56 m³·mol^-1	ChemAxon
Polarizability	37.17 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Not Available

Biological Properties

Cellular Locations

Membrane

Biofluid Locations

Blood
Urine

Tissue Location

Not Available

Pathways

Not Available

Normal Concentrations

Biofluid	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Expected but not Quantified	Not Applicable	Not Available	Not Available	Taking drug identified by DrugBank entry DB05271	Not Applicable	details
Urine	Expected but not Quantified	Not Applicable	Not Available	Not Available	Taking drug identified by DrugBank entry DB05271	Not Applicable	details

Abnormal Concentrations

Not Available

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

DB05271

DrugBank Metabolite ID

Not Available

Phenol Explorer Compound ID

Not Available

Phenol Explorer Metabolite ID

Not Available

FoodDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

51867

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Rotigotine

NuGOwiki Link

HMDB15615

Metagene Link

HMDB15615

METLIN ID

Not Available

PubChem Compound

57537

PDB ID

Not Available

ChEBI ID

Not Available

References

Synthesis Reference

Not Available

Material Safety Data Sheet (MSDS)

Not Available

General References

Giladi N, Boroojerdi B, Korczyn AD, Burn DJ, Clarke CE, Schapira AH: Rotigotine transdermal patch in early Parkinson's disease: a randomized, double-blind, controlled study versus placebo and ropinirole. Mov Disord. 2007 Dec;22(16):2398-404. [PubMed:17935234 ]
Chen JJ, Swope DM, Dashtipour K, Lyons KE: Transdermal rotigotine: a clinically innovative dopamine-receptor agonist for the management of Parkinson's disease. Pharmacotherapy. 2009 Dec;29(12):1452-67. doi: 10.1592/phco.29.12.1452. [PubMed:19947805 ]
Perez-Lloret S, Rey MV, Ratti PL, Rascol O: Rotigotine transdermal patch for the treatment of Parkinson's Disease. Fundam Clin Pharmacol. 2013 Feb;27(1):81-95. doi: 10.1111/j.1472-8206.2012.01028.x. Epub 2012 Feb 9. [PubMed:22320451 ]
de Biase S, Merlino G, Lorenzut S, Valente M, Gigli GL: ADMET considerations for restless leg syndrome drug treatments. Expert Opin Drug Metab Toxicol. 2012 Oct;8(10):1247-61. doi: 10.1517/17425255.2012.708023. Epub 2012 Jul 18. [PubMed:22808933 ]

Enzymes

Enzyme Details

1. Cytochrome P450 3A4

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:: CYP3A4
Uniprot ID:: P08684
Molecular weight:: 57255.585

References

Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]

Enzyme Details

2. Cytochrome P450 2D6

General function:: Involved in monooxygenase activity
Specific function:: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:: CYP2D6
Uniprot ID:: P10635
Molecular weight:: 55768.94

References

Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]

Enzyme Details

3. Cytochrome P450 1A2

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:: CYP1A2
Uniprot ID:: P05177
Molecular weight:: 58406.915

References

Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]

Enzyme Details

4. D(2) dopamine receptor

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
Gene Name:: DRD2
Uniprot ID:: P14416
Molecular weight:: 50618.9

References

Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]

Enzyme Details

5. D(4) dopamine receptor

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
Gene Name:: DRD4
Uniprot ID:: P21917
Molecular weight:: 48359.9

References

Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]

Enzyme Details

6. 5-hydroxytryptamine receptor 1A

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity
Gene Name:: HTR1A
Uniprot ID:: P08908
Molecular weight:: 46106.3

References

Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]

Enzyme Details

7. D(3) dopamine receptor

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation
Gene Name:: DRD3
Uniprot ID:: P35462
Molecular weight:: 44224.3

References

Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]

Enzyme Details

8. D(1A) dopamine receptor

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase
Gene Name:: DRD1
Uniprot ID:: P21728
Molecular weight:: 49292.8

References

Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]

Enzyme Details

9. D(1B) dopamine receptor

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase
Gene Name:: DRD5
Uniprot ID:: P21918
Molecular weight:: 52950.5

References

Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]

Showing metabocard for Rotigotine (HMDB15615)

Structure for HMDB15615 (Rotigotine)

Enzymes

References

References

References

References

References

References

References

References

References