rotigotine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
dopamine receptor agonists, ergoline derivatives 2407 99755-59-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • rotigotine
  • neupro
  • leganto
  • (S)-(-)-Rotigotine
Rotigotine is a non-ergoline dopamine agonist. The precise mechanism of action of rotigotine as a treatment for Parkinson's disease is unknown, although it is thought to be related to its ability to stimulate dopamine receptors within the caudate-putamen in the brain. 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 receptors.
  • Molecular weight: 315.48
  • Formula: C19H25NOS
  • CLOGP: 4.54
  • LIPINSKI: 0
  • HAC: 2
  • HDO: 1
  • TPSA: 23.47
  • ALOGS: -4.54
  • ROTB: 6

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
6 mg TD

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 5.60 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.36 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 5.70 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 37 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.08 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 4 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
May 9, 2007 FDA UCB INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Dyskinesia 154.75 21.75 71 4942 28854 46652195
Application site pruritus 102.08 21.75 31 4982 3982 46677067
Application site erythema 100.05 21.75 32 4981 4872 46676177
Hallucination 74.00 21.75 53 4960 49898 46631151
Fall 71.65 21.75 127 4886 328970 46352079
Application site reaction 63.73 21.75 15 4998 724 46680325
Choking 59.08 21.75 25 4988 8351 46672698
Anosmia 57.56 21.75 20 4993 3924 46677125
Dysphagia 57.52 21.75 55 4958 77257 46603792
Hallucination, visual 57.25 21.75 31 4982 17842 46663207
Orthostatic intolerance 57.09 21.75 15 4998 1139 46679910
Dropped head syndrome 56.40 21.75 10 5003 112 46680937
Dopamine dysregulation syndrome 54.13 21.75 11 5002 265 46680784
Stoma site pain 53.24 21.75 14 4999 1066 46679983
Product adhesion issue 53.11 21.75 20 4993 4935 46676114
Therapeutic response shortened 52.17 21.75 20 4993 5179 46675870
Micturition urgency 50.74 21.75 22 4991 7795 46673254
Loss of consciousness 50.34 21.75 60 4953 108178 46572871
Decreased interest 49.95 21.75 17 4996 3135 46677914
Nocturia 46.05 21.75 20 4993 7112 46673937
On and off phenomenon 44.78 21.75 14 4999 1977 46679072
Oromandibular dystonia 43.47 21.75 10 5003 436 46680613
Nightmare 42.86 21.75 25 4988 16573 46664476
Restless legs syndrome 41.27 21.75 24 4989 15819 46665230
Sleep talking 40.41 21.75 11 5002 956 46680093
Drooling 38.23 21.75 14 4999 3195 46677854
Application site vesicles 35.90 21.75 11 5002 1453 46679596
Stoma site inflammation 35.41 21.75 9 5004 599 46680450
Tremor 35.05 21.75 52 4961 115587 46565462
Sexual dysfunction 34.35 21.75 12 5001 2391 46678658
Drug dose titration not performed 33.89 21.75 8 5005 391 46680658
Gastrointestinal motility disorder 33.70 21.75 14 4999 4464 46676585
Application site rash 33.50 21.75 12 5001 2570 46678479
Depressed mood 33.25 21.75 28 4985 33291 46647758
Compulsive shopping 33.02 21.75 9 5004 786 46680263
Stoma site discharge 32.85 21.75 11 5002 1929 46679120
Middle insomnia 31.85 21.75 17 4996 9498 46671551
Freezing phenomenon 31.61 21.75 10 5003 1467 46679582
Weight abnormal 31.29 21.75 9 5004 956 46680093
Muscle rigidity 31.12 21.75 17 4996 9944 46671105
Antidiuretic hormone abnormality 30.83 21.75 5 5008 31 46681018
Disturbance in attention 30.42 21.75 26 4987 31534 46649515
Pneumonia aspiration 30.39 21.75 26 4987 31579 46649470
Sudden onset of sleep 30.05 21.75 8 5005 639 46680410
Ageusia 28.88 21.75 17 4996 11455 46669594
Bradykinesia 28.50 21.75 12 5001 3954 46677095
Stoma site infection 28.07 21.75 8 5005 822 46680227
Somnolence 27.16 21.75 55 4958 156466 46524583
Anxiety 25.90 21.75 59 4954 181898 46499151
Reduced facial expression 25.03 21.75 8 5005 1212 46679837
Impulse-control disorder 24.78 21.75 7 5006 697 46680352
Constipation 24.27 21.75 56 4957 174041 46507008
Delusion 24.09 21.75 15 4998 11173 46669876
Wrong technique in product usage process 23.35 21.75 29 4984 54393 46626656
Device adhesion issue 23.24 21.75 9 5004 2393 46678656
Dermatitis contact 23.01 21.75 13 5000 8110 46672939
Panic disorder 22.68 21.75 9 5004 2552 46678497
Psychotic disorder 22.54 21.75 19 4994 22602 46658447
Altered state of consciousness 22.02 21.75 19 4994 23329 46657720
Akinesia 21.98 21.75 8 5005 1793 46679256
Application site irritation 21.90 21.75 8 5005 1811 46679238
Application site dermatitis 21.87 21.75 5 5008 212 46680837

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
On and off phenomenon 201.67 23.35 56 5856 2835 29943731
Hallucination 200.42 23.35 123 5789 48936 29897630
Dyskinesia 149.75 23.35 77 5835 21757 29924809
Impulse-control disorder 125.31 23.35 33 5879 1362 29945204
Freezing phenomenon 105.74 23.35 31 5881 1905 29944661
Hallucination, visual 102.33 23.35 54 5858 16059 29930507
Application site erythema 92.04 23.35 29 5883 2274 29944292
Application site pruritus 83.76 23.35 24 5888 1359 29945207
Application site reaction 83.32 23.35 19 5893 425 29946141
Choking 80.73 23.35 32 5880 4914 29941652
Dysphagia 79.22 23.35 75 5837 56623 29889943
Bradykinesia 74.84 23.35 27 5885 3203 29943363
Restless legs syndrome 70.59 23.35 32 5880 6840 29939726
Anosmia 69.83 23.35 23 5889 2077 29944489
Micturition urgency 66.68 23.35 27 5885 4380 29942186
Poor quality sleep 65.89 23.35 31 5881 7210 29939356
Sleep talking 60.87 23.35 15 5897 472 29946094
Delusion 59.06 23.35 34 5878 11955 29934611
Tremor 58.29 23.35 73 5839 75290 29871276
Middle insomnia 56.51 23.35 26 5886 5747 29940819
Nocturia 56.00 23.35 29 5883 8283 29938283
Muscle rigidity 52.96 23.35 30 5882 10231 29936335
Hypersexuality 52.32 23.35 17 5895 1470 29945096
Stoma site discharge 52.17 23.35 17 5895 1484 29945082
Parkinson's disease 49.82 23.35 17 5895 1711 29944855
Fall 49.55 23.35 110 5802 181762 29764804
Mobility decreased 49.45 23.35 41 5871 25958 29920608
Gastrointestinal motility disorder 49.10 23.35 18 5894 2233 29944333
Application site rash 48.47 23.35 14 5898 815 29945751
Therapeutic response shortened 44.18 23.35 19 5893 3581 29942985
Device dislocation 44.11 23.35 21 5891 5010 29941556
Pneumonia aspiration 43.47 23.35 45 5867 37735 29908831
Libido decreased 42.93 23.35 20 5892 4546 29942020
Dropped head syndrome 41.84 23.35 8 5904 72 29946494
Balance disorder 41.14 23.35 43 5869 36450 29910116
Memory impairment 40.48 23.35 43 5869 37131 29909435
Initial insomnia 39.63 23.35 16 5896 2573 29943993
Libido increased 39.50 23.35 12 5900 832 29945734
Depressed mood 39.09 23.35 30 5882 16999 29929567
Stoma site erythema 36.99 23.35 12 5900 1032 29945534
Product adhesion issue 36.78 23.35 13 5899 1452 29945114
Dystonia 36.07 23.35 23 5889 9704 29936862
Device kink 34.91 23.35 10 5902 565 29946001
Application site vesicles 34.60 23.35 10 5902 583 29945983
Stoma site inflammation 34.26 23.35 10 5902 604 29945962
Drooling 34.07 23.35 15 5897 2990 29943576
Gambling disorder 33.89 23.35 13 5899 1827 29944739
Posture abnormal 33.73 23.35 13 5899 1851 29944715
Akinesia 33.34 23.35 14 5898 2486 29944080
Dermatitis allergic 32.84 23.35 18 5894 5754 29940812
Stoma site pain 32.72 23.35 10 5902 708 29945858
Hyperkinesia 32.23 23.35 13 5899 2085 29944481
Device occlusion 31.86 23.35 18 5894 6102 29940464
Decreased interest 31.67 23.35 13 5899 2182 29944384
Nightmare 31.56 23.35 23 5889 12053 29934513
Stress 30.57 23.35 28 5884 20207 29926359
Stoma site hypergranulation 30.27 23.35 8 5904 334 29946232
Skin swelling 29.99 23.35 10 5902 937 29945629
Musculoskeletal stiffness 29.69 23.35 36 5876 35845 29910721
Sexual dysfunction 29.49 23.35 17 5895 5984 29940582
Application site irritation 28.52 23.35 9 5903 708 29945858
Gait disturbance 27.11 23.35 51 5861 74726 29871840
Tricuspid valve sclerosis 26.68 23.35 5 5907 40 29946526
Therapeutic product effect variable 26.25 23.35 10 5902 1379 29945187
Stoma site infection 26.03 23.35 9 5903 942 29945624
Mucosal haemorrhage 25.78 23.35 10 5902 1448 29945118
Sexually inappropriate behaviour 25.60 23.35 7 5905 333 29946233
Ageusia 25.57 23.35 18 5894 8935 29937631
Anxiety 25.09 23.35 55 5857 89816 29856750
Speech disorder 24.30 23.35 27 5885 24485 29922081
Polycythaemia 24.00 23.35 10 5902 1742 29944824
Compulsive shopping 23.69 23.35 7 5905 441 29946125

Pharmacologic Action:

SourceCodeDescription
ATC N04BC09 NERVOUS SYSTEM
ANTI-PARKINSON DRUGS
DOPAMINERGIC AGENTS
Dopamine agonists
MeSH PA D015259 Dopamine Agents
MeSH PA D018491 Dopamine Agonists
MeSH PA D018377 Neurotransmitter Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Restless legs indication 32914008 DOID:0050425
Parkinson's disease indication 49049000 DOID:14330
Dyskinesia contraindication 9748009
Orthostatic hypotension contraindication 28651003
Hypertensive disorder contraindication 38341003 DOID:10763
Body fluid retention contraindication 43498006
Chronic heart failure contraindication 48447003
Acute nephropathy contraindication 58574008
Magnetic resonance imaging contraindication 113091000
Syncope contraindication 271594007
Drowsy contraindication 271782001
Peripheral edema contraindication 271809000
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.6 acidic
pKa2 8.87 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
D(2) dopamine receptor GPCR AGONIST Ki 10.22 IUPHAR IUPHAR
D(1A) dopamine receptor GPCR AGONIST Ki 5.60 IUPHAR
D(3) dopamine receptor GPCR AGONIST Ki 8.40 IUPHAR
D(4) dopamine receptor GPCR AGONIST Ki 7.26 CHEMBL
D(1B) dopamine receptor GPCR AGONIST Ki 6 IUPHAR
D(1A) dopamine receptor GPCR Ki 6.30 CHEMBL
D(2) dopamine receptor GPCR Ki 7.82 CHEMBL

External reference:

IDSource
4025266 VUID
N0000171794 NUI
D05768 KEGG_DRUG
4025266 VANDF
C1949346 UMLSCUI
CHEBI:135351 CHEBI
CHEMBL1303 ChEMBL_ID
C047508 MESH_SUPPLEMENTAL_RECORD_UI
941 IUPHAR_LIGAND_ID
7897 INN_ID
DB05271 DRUGBANK_ID
87T4T8BO2E UNII
59227 PUBCHEM_CID
616739 RXNORM
21751 MMSL
83818 MMSL
d05848 MMSL
011270 NDDF
421915002 SNOMEDCT_US
421924006 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Neupro HUMAN PRESCRIPTION DRUG LABEL 1 50474-801 PATCH, EXTENDED RELEASE 1 mg TRANSDERMAL NDA 31 sections
Neupro HUMAN PRESCRIPTION DRUG LABEL 1 50474-802 PATCH, EXTENDED RELEASE 2 mg TRANSDERMAL NDA 31 sections
Neupro HUMAN PRESCRIPTION DRUG LABEL 1 50474-803 PATCH, EXTENDED RELEASE 3 mg TRANSDERMAL NDA 31 sections
Neupro HUMAN PRESCRIPTION DRUG LABEL 1 50474-804 PATCH, EXTENDED RELEASE 4 mg TRANSDERMAL NDA 31 sections
Neupro HUMAN PRESCRIPTION DRUG LABEL 1 50474-805 PATCH, EXTENDED RELEASE 6 mg TRANSDERMAL NDA 31 sections
Neupro HUMAN PRESCRIPTION DRUG LABEL 1 50474-806 PATCH, EXTENDED RELEASE 8 mg TRANSDERMAL NDA 31 sections