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Pergolide

PubChem CID
47811
Structure
Pergolide_small.png
Pergolide_3D_Structure.png
Molecular Formula
Synonyms
  • pergolide
  • 66104-22-1
  • Permax
  • Pergolida
  • Pergolidum
Molecular Weight
314.5 g/mol
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Dates
  • Create:
    2005-03-26
  • Modify:
    2025-02-01
Description
Pergolide is a diamine that is ergoline in which the beta-hydrogen at position 8 is replaced by a (methylthio)methyl group and the hydrogen attached to the piperidine nitrogen (position 6) is replaced by a propyl group. A dopamine D2 receptor agonist which also has D1 and D2 agonist properties, it is used as the mesylate salt in the management of Parkinson's disease, although it was withdrawn from the U.S. and Canadian markets in 2007 due to an increased risk of cardiac valve dysfunction. It has a role as an antiparkinson drug and a dopamine agonist. It is a diamine, an organic heterotetracyclic compound and a methyl sulfide. It is a conjugate base of a pergolide(1+).
Pergolide is a long-acting dopamine agonist approved in 1982 for the treatment of Parkinson’s Disease. It is an ergot derivative that acts on the dopamine D2 and D3, alpha2- and alpha1-adrenergic, and 5-hydroxytryptamine (5-HT) receptors. It was indicated as adjunct therapy with levodopa/carbidopa in the symptomatic treatment of parkinsonian syndrome. It was later found that pergolide increased the risk of cardiac valvulopathy. The drug was withdrawn from the US market in March 2007 and from the Canadian market in August 2007. While the use of pergolide in humans is still approved in only some countries, pergolide is mainly used for veterinary purposes.
Pergolide is an Ergot-derived Dopamine Receptor Agonist. The mechanism of action of pergolide is as a Dopamine Agonist.
See also: Pergolide Mesylate (has salt form).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Pergolide.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(6aR,9R,10aR)-9-(methylsulfanylmethyl)-7-propyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline
Computed by Lexichem TK 2.7.0 (PubChem release 2024.11.20)

2.1.2 InChI

InChI=1S/C19H26N2S/c1-3-7-21-11-13(12-22-2)8-16-15-5-4-6-17-19(15)14(10-20-17)9-18(16)21/h4-6,10,13,16,18,20H,3,7-9,11-12H2,1-2H3/t13-,16-,18-/m1/s1
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.3 InChIKey

YEHCICAEULNIGD-MZMPZRCHSA-N
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.4 SMILES

CCCN1C[C@@H](C[C@H]2[C@H]1CC3=CNC4=CC=CC2=C34)CSC
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C19H26N2S
Computed by PubChem 2.2 (PubChem release 2024.11.20)

2.3 Other Identifiers

2.3.1 CAS

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 HMDB ID

2.3.10 KEGG ID

2.3.11 Metabolomics Workbench ID

2.3.12 NCI Thesaurus Code

2.3.13 Nikkaji Number

2.3.14 PharmGKB ID

2.3.15 Pharos Ligand ID

2.3.16 RXCUI

2.3.17 Wikidata

2.3.18 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Celance
  • LY-127,809
  • LY-127809
  • LY127,809
  • LY127809
  • Mesylate, Pergolide
  • Parkotil
  • Pergolide
  • Pergolide Mesylate
  • Permax
  • Pharken

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
314.5 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
XLogP3-AA
Property Value
4.2
Reference
Computed by XLogP3 3.0 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Acceptor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Rotatable Bond Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Exact Mass
Property Value
314.18167001 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Monoisotopic Mass
Property Value
314.18167001 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Topological Polar Surface Area
Property Value
44.3 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Heavy Atom Count
Property Value
22
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
388
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
3
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Solid

3.2.2 Melting Point

207.5 °C
PhysProp
207.5 °C

3.2.3 Solubility

5.84e-04 g/L

3.2.4 LogP

4
4

3.2.5 Collision Cross Section

177.9 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.3.1.1 Human Drugs
Human drug -> Discontinued
Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664
3.3.1.2 Animal Drugs
Pharmaceuticals -> UK Veterinary Medicines Directorate List
S104 | UKVETMED | UK Veterinary Medicines Directorate's List | DOI:10.5281/zenodo.7802119

4 Spectral Information

4.1 1D NMR Spectra

1D NMR Spectra

4.1.1 13C NMR Spectra

Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
Thumbnail
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 2
Copyright
Copyright © 2020-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
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2 of 2
Technique
GC/MS
Source of Spectrum
DigiLab GmbH (C) 2024
Copyright
Copyright © 2024 DigiLab GmbH and Wiley-VCH GmbH. All Rights Reserved.
Thumbnail
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4.2.2 MS-MS

1 of 6
View All
Spectra ID
Instrument Type
LC-ESI-QTOF
Ionization Mode
positive
Top 5 Peaks

315.1869 100

208.1108 3.87

267.1818 0.77

193.087 0.76

154.0645 0.75

Thumbnail
Thumbnail
Notes
instrument=Agilent 1200 RRLC; Agilent 6520 QTOF
2 of 6
View All
Spectra ID
Instrument Type
LC-ESI-QTOF
Ionization Mode
positive
Top 5 Peaks

315.1871 100

208.1107 56.42

167.0706 8.95

154.0644 8.31

196.1108 7.60

Thumbnail
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Notes
instrument=Agilent 1200 RRLC; Agilent 6520 QTOF

4.2.3 LC-MS

1 of 9
View All
Authors
Cuthbertson DJ, Johnson SR, Lange BM, Institute of Biological Chemistry, Washington State University
Instrument
Agilent 1200 RRLC; Agilent 6520 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Collision Energy
10 ev
Column Name
Agilent C8 Cartridge Column 2.1X30mm 3.5 micron (guard); Agilent SB-Aq 2.1x50mm 1.8 micron (analytical)
Retention Time
5.397
Precursor m/z
315.189
Precursor Adduct
[M+H]+
Top 5 Peaks

315.1869 999

208.1108 39

267.1818 8

193.087 8

154.0645 8

Thumbnail
Thumbnail
License
CC BY-SA
2 of 9
View All
Authors
Cuthbertson DJ, Johnson SR, Lange BM, Institute of Biological Chemistry, Washington State University
Instrument
Agilent 1200 RRLC; Agilent 6520 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Collision Energy
20 ev
Column Name
Agilent C8 Cartridge Column 2.1X30mm 3.5 micron (guard); Agilent SB-Aq 2.1x50mm 1.8 micron (analytical)
Retention Time
5.397
Precursor m/z
315.189
Precursor Adduct
[M+H]+
Top 5 Peaks

315.1871 999

208.1107 564

167.0706 89

154.0644 83

196.1108 76

Thumbnail
Thumbnail
License
CC BY-SA

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Indicated as adjunctive treatment to levodopa/carbidopa in the management of the signs and symptoms of Parkinson's disease. It was withdrawn from the US and Canadian markets in 2007 due to an increased risk of cardiac valvulopathy.

7.2 LiverTox Summary

Pergolide is an oral dopamine receptor agonist used predominantly in the therapy of Parkinson disease. Pergolide therapy is associated with low rate of transient serum enzyme elevations during treatment and has been implicated in rare cases of acute liver injury.

7.3 Drug Classes

Antiparkinson Agents

7.4 Drug Labels

Drug and label
Active ingredient and drug

7.5 Clinical Trials

7.5.1 ClinicalTrials.gov

7.5.2 EU Clinical Trials Register

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Pergolide stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1 and D5 subreceptors and are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3 and D4 subreceptors and has been associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2 and D3 receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2 stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2 stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2- and D3-receptors. It also exhibits agonist activity on dopamine D4, D1, and D5, 5-hydroxytryptamine (5-HT)1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, α2A-, α2B-, α2C-, α1A-, α1B-, and α1D-adrenergic receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2A agonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion. Pergolide also causes transient increases in somatotropin (growth hormone) secretion and decreases in luteinizing hormone (LH) concentrations.

8.2 MeSH Pharmacological Classification

Dopamine Agonists
Drugs that bind to and activate dopamine receptors. (See all compounds classified as Dopamine Agonists.)

8.3 FDA Pharmacological Classification

FDA UNII
24MJ822NZ9
Active Moiety
PERGOLIDE
Pharmacological Classes
Mechanisms of Action [MoA] - Dopamine Agonists
Pharmacological Classes
Chemical Structure [CS] - Ergot Alkaloids
Pharmacological Classes
Established Pharmacologic Class [EPC] - Ergot-derived Dopamine Receptor Agonist
FDA Pharmacology Summary
Pergolide is an Ergot-derived Dopamine Receptor Agonist. The mechanism of action of pergolide is as a Dopamine Agonist.

8.4 ATC Code

N - Nervous system

N04 - Anti-parkinson drugs

N04B - Dopaminergic agents

N04BC - Dopamine agonists

N04BC02 - Pergolide

8.5 Absorption, Distribution and Excretion

Absorption
Significant amount may be absorbed (evidence on bioavailability still lacking).
Route of Elimination
The major route of excretion is the kidney.

8.6 Metabolism / Metabolites

Extensively hepatic.
Pergolide undergoes extensive first-pass hepatic metabolism and its metabolism are excreted mainly in the urine. (A2932) Route of Elimination: The major route of excretion is the kidney. Half Life: 27 hours
A2932: Blin O: The pharmacokinetics of pergolide in Parkinson's disease. Curr Opin Neurol. 2003 Dec;16 Suppl 1:S9-12. PMID:15180132

8.7 Biological Half-Life

27 hours

8.8 Mechanism of Action

The dopamine D2 receptor is a 7-transmembrane G-protein coupled receptor associated with Gi proteins. In lactotrophs, stimulation of dopamine D2 receptor causes inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP3-dependent release of Ca2+ from intracellular stores. Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gated calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p42/p44 MAPK and decreases MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition. Stimulation of dopamine D2 receptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders.

8.9 Human Metabolite Information

8.9.1 Cellular Locations

Membrane

9 Use and Manufacturing

9.1 Uses

Indicated as adjunctive treatment to levodopa/carbidopa in the management of the signs and symptoms of Parkinson's disease. It was withdrawn from the US and Canadian markets in 2007 due to an increased risk of cardiac valvulopathy. Pergolide is an ergoline-based, long-acting dopamine agonist which is effective in the treatment of Parkinson's disease and hyperprolactinemia. It has also been observed to have antihypertensive effects. Ergoline alkaloids occurs in various species of vines of the Convolvulaceae (morning glory) family and in some species of lower fungi. (L1918, L1929)
L1918: Wikipedia. Ergoline. Last Updated 2 April 2010. http://en.wikipedia.org/wiki/Ergoline
L1929: Wikipedia. Pergolide. Last Updated 15 March 2010. http://en.wikipedia.org/wiki/Pergolide

9.1.1 Use Classification

Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

Pictogram(s)
Acute Toxic
Health Hazard
Signal
Danger
GHS Hazard Statements

H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]

H351 (100%): Suspected of causing cancer [Warning Carcinogenicity]

H361 (100%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

Precautionary Statement Codes

P203, P264, P270, P280, P301+P316, P318, P321, P330, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary
The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

10.1.2 Hazard Classes and Categories

Acute Tox. 2 (100%)

Carc. 2 (100%)

Repr. 2 (100%)

11 Toxicity

11.1 Toxicological Information

11.1.1 Toxicity Summary

The dopamine D2 receptor is a 7-transmembrane G-protein coupled receptor associated with Gi proteins. In lactotrophs, stimulation of dopamine D2 receptor causes inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP3-dependent release of Ca2+ from intracellular stores. Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gated calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p42/p44 MAPK and decreases MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition. Stimulation of dopamine D2 receptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders. Ergoline alkaloids have been shown to have the significant affinity towards the 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and alpha-adrenergic receptors. This can result in a number of different effects, including vasoconstriction, convulsions, and hallucinations. Pergolide is a potent dopamine receptor agonist. It directly stimulates post-synaptic dopamine receptors at both D1 and D2 receptor sites in the nigrostriatal system. This can reduce the motor complications associated with Parkinson's. Agonism of 5-HT2B and 5-HT1B receptors is believed to be responsible for the fibrotic reactions and cardiac valvular disease associated with pergolide use. (A365, A2933, A2934, A2914, A2915, A2916)
A2914: Mantegani S, Brambilla E, Varasi M: Ergoline derivatives: receptor affinity and selectivity. Farmaco. 1999 May 30;54(5):288-96. PMID:10418123
A2915: Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. PMID:17149427
A2916: Kvernmo T, Hartter S, Burger E: A review of the receptor-binding and pharmacokinetic properties of dopamine agonists. Clin Ther. 2006 Aug;28(8):1065-78. PMID:16982285
A2933: Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. PMID:18691132
A2934: Jenner P: Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson's disease. Curr Opin Neurol. 2003 Dec;16 Suppl 1:S3-7. PMID:15180131
A365: Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. PMID:11752352

11.1.2 Hepatotoxicity

Pergolide has been reported to cause serum aminotransferase elevations in a small proportion of patients, but these abnormalities are usually mild, asymptomatic and self-limiting even without dose adjustment. In addition, pergolide has been implicated in a small number of cases of clinically apparent, acute liver injury, but the frequency, severity, clinical characteristics and typical pattern of enzyme elevations have not been characterized. Thus, pergolide is may be a rare cause of clinically apparent liver injury.

Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).

11.1.3 Drug Induced Liver Injury

Compound
pergolide
DILI Annotation
Ambiguous DILI-concern
Severity Grade
3
Label Section
Adverse reactions
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

11.1.4 Carcinogen Classification

Carcinogen Classification
No indication of carcinogenicity to humans (not listed by IARC).

11.1.5 Health Effects

Ingestion of ergoline alkaloids is known to cause the disease ergotism. Ergotism occurs in two forms, gangrenous and convulsive, likely depending on the different kinds and amounts of ergoline alkaloids present. The use of pergolide has been shown to increase the risk of cardiac valvular disease. It also increases the risk of fibrotic complications including pulmonary, pleural, and/or retroperitoneal fibrosis, pericarditis, pleuritis, and pericardial and/or pleural effusions. (A2913, L1570)

11.1.6 Exposure Routes

Oral (L1929)
L1929: Wikipedia. Pergolide. Last Updated 15 March 2010. http://en.wikipedia.org/wiki/Pergolide

11.1.7 Symptoms

Symptoms of pergolide overdose include nausea, vomiting, convulsions, decreased blood pressure, and CNS stimulation. Convulsive ergotism can cause painful seizures and spasms, diarrhea, paresthesias, itching, headaches, nausea and vomiting. Usually the gastrointestinal effects precede the central nervous system effects. As well as seizures there can be hallucinations and mental effects including mania or psychosis. Gangrenous ergotism causes dry gangrene as a result of vasoconstriction induced in the more poorly vascularized distal structures, such as the fingers and toes. Symptoms include desquamation, weak periphery pulse, loss of peripheral sensation, edema and ultimately the death and loss of affected tissues. (L1920, L1570)
L1920: Wikipedia. Ergotism. Last Updated 6 April 2010. http://en.wikipedia.org/wiki/Ergotism

11.1.8 Toxicity Data

LD50: 15 mg/kg (Oral, Rat) (A308)
A308: Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. PMID:18048412

11.1.9 Treatment

Management of overdosage may require supportive measures to maintain arterial blood pressure. Cardiac function should be monitored; an antiarrhythmic agent may be necessary. If signs of CNS stimulation are present, a phenothiazine or other butvronhenone neuroleptic agent may be indicated; the efficacy of such drugs in reversing the effects of overdose has not been assessed. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Treatment for ergotism consists of vasodilators, anticoagulants and low molecular weight dextrans. If necessary, a sympathetic nerve blockade may be carried out, such as brachial plexus blockade. Temporary sedation (e.g. haloperidol) will be necessary in hallucination and diazepam is used for convulsions. There is no specific antidote. (L1921, L1930)
L1921: Van den Enden, E. (2004). Illustrated Lecture Notes on Tropical Medicine. http://www.itg.be/evde/
L1930: RxList: The Internet Drug Index (2010). Permax (Pergolide). http://www.rxlist.com/permax-drug.htm

11.1.10 Protein Binding

90%

12 Associated Disorders and Diseases

13 Literature

13.1 Consolidated References

13.2 NLM Curated PubMed Citations

13.3 Springer Nature References

13.4 Thieme References

13.5 Nature Journal References

13.6 Chemical Co-Occurrences in Literature

13.7 Chemical-Gene Co-Occurrences in Literature

13.8 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 WIPO PATENTSCOPE

14.3 Chemical Co-Occurrences in Patents

14.4 Chemical-Disease Co-Occurrences in Patents

14.5 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Chemical-Target Interactions

15.2 Drug-Drug Interactions

15.3 Drug-Food Interactions

Take with or without food.

16 Biological Test Results

16.1 BioAssay Results

17 Classification

17.1 MeSH Tree

17.2 NCI Thesaurus Tree

17.3 ChEBI Ontology

17.4 KEGG: ATC

17.5 KEGG: Target-based Classification of Drugs

17.6 KEGG: Drug Groups

17.7 WHO ATC Classification System

17.8 FDA Pharm Classes

17.9 ChemIDplus

17.10 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

17.11 ChEMBL Target Tree

17.12 UN GHS Classification

17.13 NORMAN Suspect List Exchange Classification

17.14 CCSBase Classification

17.15 EPA DSSTox Classification

17.16 MolGenie Organic Chemistry Ontology

18 Information Sources

  1. CAS Common Chemistry
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    https://creativecommons.org/licenses/by-nc/4.0/
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
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    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  4. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  5. European Chemicals Agency (ECHA)
    LICENSE
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    https://echa.europa.eu/web/guest/legal-notice
  6. FDA Global Substance Registration System (GSRS)
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    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  7. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  8. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  9. ChEBI
  10. FDA Pharm Classes
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  11. LiverTox
  12. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  13. Toxin and Toxin Target Database (T3DB)
    LICENSE
    T3DB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (T3DB) and the original publication.
    http://www.t3db.ca/downloads
  14. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  15. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  16. DailyMed
  17. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
    [DES-PRO8,DES-PHE9,DES-ARG10]KALLIDIN
    https://www.dgidb.org/drugs/iuphar.ligand:648
  18. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
    The Guide to PHARMACOLOGY database is licensed under the Open Data Commons Open Database License (ODbL) https://opendatacommons.org/licenses/odbl/. Its contents are licensed under a Creative Commons Attribution-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-sa/4.0/)
    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  19. Therapeutic Target Database (TTD)
  20. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  21. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  22. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Pergolide
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  23. EU Clinical Trials Register
  24. Japan Chemical Substance Dictionary (Nikkaji)
  25. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
  26. MassBank Europe
  27. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  28. Metabolomics Workbench
  29. Nature Chemical Biology
  30. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  31. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  32. NMRShiftDB
  33. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  34. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  35. SpectraBase
    8-[(Methylsulfanyl)methyl]-6-propylergoline
    https://spectrabase.com/spectrum/Jh8St4dypAG
  36. Springer Nature
  37. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  38. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  39. Wikidata
  40. Wikipedia
  41. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  42. PubChem
  43. GHS Classification (UNECE)
  44. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  45. PATENTSCOPE (WIPO)
  46. NCBI
CONTENTS