ROTIGOTINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H25NOS
Molecular Weight	315.473
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CCCN(CCC1=CC=CS1)[C@H]2CCC3=C(O)C=CC=C3C2

InChI

InChIKey=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

HIDE SMILES / InChI

Molecular Formula	C19H25NOS
Molecular Weight	315.473
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

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. It is FDA approved for the treatment of Parkinson's disease, restless legs syndrome. Dopamine antagonists, such as antipsychotics or metoclopramide, may diminish the effectiveness of Rotigotine. Common adverse reactions include nausea, vomiting, somnolence, application site reactions, dizziness, anorexia, hyperhidrosis, insomnia and dyskinesia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D2 receptor 311	Agonist 2,752	13.5 nM [Ki]
Dopamine D1 receptor 106	Agonist 2,752	83.0 nM [Ki]
Dopamine D5 receptor 15	Agonist 2,752	5.4 nM [Ki]
Dopamine D4 receptor 76	Agonist 2,752	15.0 nM [Ki]
Serotonin 1a (5-HT1a) receptor 177	Agonist 2,752	30.0 nM [Ki]
Alpha-2b adrenergic receptor 35	Antagonist 2,849	27.0 nM [Ki]
Dopamine D3 receptor 97	Agonist 2,752	0.7 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Parkinson's disease 232	Primary		Approved 8,583	NEUPRO
Restless legs syndrome 17	Primary		Approved 8,583	NEUPRO

C_max

Value	Dose	Co-administered	Analyte	Population
0.34 ng/mL	3 mg 2 times / day steady-state, transdermal		ROTIGOTINE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
4.63 ng × h/mL	3 mg 2 times / day steady-state, transdermal		ROTIGOTINE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.5 h	3 mg 2 times / day steady-state, transdermal		ROTIGOTINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
10%	unknown		ROTIGOTINE plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2,252 inducer 1,087 substrate 1,946	inhibitor 2,438 inducer 440	inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2,153 CYP2C19 2,057 P-gp 1,741	UGT1A9 423 UGT2B15 236 CYP2C19 1,119 SULT1A3 31 UGT1A1 479 UGT1A3 470 UGT1A4 399 UGT1A6 343 UGT1A7 249 UGT2B4 278 UGT2B7 456 UGT2B17 237 UGT1A8 323 UGT1A10 331 CYP1A2 1,197	CYP1A2 832 CYP2C19 329

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 2,333	inducer 1,966	no
CYP1A2 2,333	inhibitor 4,027	no
CYP2C19 2,141	inducer 1,966	no
CYP2C19 2,141	inhibitor 4,027	no
CYP2C9 2,497	inducer 1,966	no

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Drug as victim

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Target	Modality	Activity
UGT1A10 331	substrate 4,014	minor [Km >1000 uM]
UGT1A8 323	substrate 4,014	minor [Km >1000 uM]
UGT1A1 479	substrate 4,014	no
UGT1A3 470	substrate 4,014	no
UGT1A4 399	substrate 4,014	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
AA Blocks	AA0039VR	https://www.aablocks.com/goods/Goods/detail?id=AA0039VR
Aaron Chemicals	AR003ANJ	http://www.aaronchem.com/99755-59-6
abcr GmbH	AB462946	http://www.abcr.com/shop/en/AB462946
AbMole Bioscience	M3675	http://www.abmole.com/products/rotigotine.html
Achemtek	0102-020374	http://www.achemtek.com/99755-59-6

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PubMed

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Title	Date	PubMed
Three-month subchronic intramuscular toxicity study of rotigotine-loaded microspheres in Cynomolgus monkeys.	2013 Feb	23165154

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Patents

Sample Use Guides

In Vivo Use Guide

Parkinson’s disease: Initially, 2 mg/24 hours for early-stage disease or 4 mg/24 hours for advanced-stage disease. The dose may be increased as needed by 2 mg/24 hours at weekly intervals, up to 6 mg/24 hours for earlystage disease and up to 8 mg/24 hours for advanced-stage disease. Restless Legs Syndrome: Initially, 1 mg/24 hours, increased as needed by 1 mg/24 hours at weekly intervals, up to 3 mg/24 hours.

Route of Administration: Transdermal

In Vitro Use Guide

The binding of [3H]N-0437 (specific activity 80.6 Ci/mmol) to calf caudate membranes is described. It was found that [3H]N-0437 binds with a high affinity (KD = 0.17 nM) and a low proportion of non-specific binding.

Substance Class	Chemical
Record UNII	87T4T8BO2E
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ROTIGOTINE

Official Name

English

LEGANTO

Preferred Name

English

ROTIGOTINE [USP MONOGRAPH]

Common Name

English

ROTIGOTINE [EP MONOGRAPH]

Common Name

English

NEUPRO

Brand Name

English

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Classification Tree

Code System

Code

PARKINSONIAN DISORDERS

EMA ASSESSMENT REPORTS

NEUPRO (AUTHORIZED: PARKINSON DISEASE)

Dopamine agonists

WHO-ATC

N04BC09

PARASOMNIAS

EMA ASSESSMENT REPORTS

NEUPRO (AUTHORIZED: RESTLESS LEGS SYNDROME)

PARASOMNIAS

EMA ASSESSMENT REPORTS

LEGANTO (AUTHORIZED: RESTLESS LEGS SYNDROME)

Dopamine agonists

WHO-VATC

QN04BC09

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Code System

Code

Type

Description

USAN

QQ-05

PRIMARY

IUPHAR

941

PRIMARY

SMS_ID

100000089581

PRIMARY

INN

7897

PRIMARY

PUBCHEM

59227

PRIMARY

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Related Record

Type

Details


					87T4T8BO2E

ROTIGOTINE

EXCRETED UNCHANGED

Qualification:

URINE

Amount:

[<1] % (average)


					RI471QC62V

D(4) DOPAMINE RECEPTOR

TARGET -> AGONIST

Amount:


					50U1BO5G5P

ALPHA-2A ADRENERGIC RECEPTOR

TARGET -> AGONIST


					19GBD6T9L7

D(2) DOPAMINE RECEPTOR

TARGET -> AGONIST


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:

89.5 % (average)

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Related Record

Type

Details


					C83X2N3S59

DESTHIENYLETHYL ROTIGOTINE SULFATE

METABOLITE -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:


					Y8W64KJ2P6

N-DESPROPYL ROTIGOTINE GLUCURONIDE

METABOLITE -> PARENT

Interaction Type:

MINOR

Qualification:

URINE

Amount:


					C2T6Z2W3JW

ROTIGOTINE GLUCURONIDE

METABOLITE -> PARENT

Comments:

two UDP-glucuronosyltransferases catalyze the metabolism of rotigotine


					6638WXC8KK

N-DESPROPYL ROTIGOTINE SULFATE

METABOLITE -> PARENT

Interaction Type:

MAJOR

Qualification:

PLASMA; URINE

Amount:


					K4K6D2GA9S

ROTIGOTINE SULFATE

METABOLITE -> PARENT

Interaction Type:

MAJOR

Qualification:

PLASMA; URINE

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Type

Details


					97PH4652RU

(6S)-6-(PROPYL(2-(THIOPHEN-2-YL)ETHYL)AMINO)-5,6,7,8-TETRAHYDRONAPHTHALEN-1-YL ACETATE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

[<0.1] PERCENT PEAK AREA (limits)


					BX28WNZ8X5

(6S)-6-(ETHYL(2-(2-THIENYL)ETHYL)AMINO)-5,6,7,8-TETRAHYDRO-1-NAPHTHALENOL

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

[<0.1] PERCENT PEAK AREA (limits)


					S0A0O2B54C

DESTHIENYLETHYL ROTIGOTINE

IMPURITY -> PARENT

Comments:

below LOQ (300 dpm/ml)

Interaction Type:

MINOR

Qualification:

URINE

Amount:


					23QRX5CL2N

(2S)-N-PROPYL-5-(2-(THIOPHEN-2-YL)ETHOXY)-N-(2-(THIOPHEN-2-YL)ETHYL)-1,2,3,4-TETRAHYDRONAPHTHALEN-2-AMINE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

[<0.1] PERCENT PEAK AREA (limits)


					S0A0O2B54C

DESTHIENYLETHYL ROTIGOTINE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

[<0.15] PERCENT PEAK AREA (limits)

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Related Record

Type

Details


					87T4T8BO2E

ROTIGOTINE

ACTIVE MOIETY

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Name	Property Type	Amount
Volume of Distribution	PHARMACOKINETIC	84 Liters/Kilogram (average)

Tmax	PHARMACOKINETIC	[15 to 18] hours (average)

Biological Half-life	PHARMACOKINETIC	[5 to 7] hours (average)

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator