Pergolide (CHEM002368)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (17)XML
Record Information
Version1.0
Creation Date2009-07-21 20:28:34 UTC
Update Date2026-05-14 16:58:35 UTC
Accession NumberCHEM002368
Identification
Common NamePergolide
ClassSmall Molecule
DescriptionPergolide 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 The drug was withdrawn from the US market in March 2007 and from the Canadian market in August 2007.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
Contaminant Type
  • Amine
  • Antidyskinetic
  • Antiparkinson Agent
  • Central Nervous System Agent
  • Dopamine Agonist
  • Drug
  • Ether
  • Human Neurotoxin
  • Metabolite
  • Neuroprotective Agent
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
PergolidaChEBI
PergolidumChEBI
PermaxKegg
Pergolide methanesulfonateHMDB
Athena brand OF pergolide mesylateHMDB
Elanco brand OF pergolide mesylateHMDB
Mesylate, pergolideHMDB
Pergolide mesylateHMDB
CelanceHMDB
Lilly brand OF pergolideHMDB
ParkotilHMDB
Draxis brand OF pergolide mesylateHMDB
Lilly brand OF pergolide mesylateHMDB
PharkenHMDB
Chemical FormulaC19H26N2S
Average Molecular Mass314.488 g/mol
Monoisotopic Mass314.182 g/mol
CAS Registry Number66104-22-1
IUPAC Name(2R,4R,7R)-4-[(methylsulfanyl)methyl]-6-propyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),9,12,14-tetraene
Traditional Namepergolide
SMILES[H][C@@]12CC3=CNC4=CC=CC(=C34)[C@@]1([H])C[C@@H](CSC)CN2CCC
InChI IdentifierInChI=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
InChI KeyYEHCICAEULNIGD-MZMPZRCHSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as indoloquinolines. These are polycyclic aromatic compounds containing an indole fused to a quinoline.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassIndoloquinolines
Direct ParentIndoloquinolines
Alternative Parents
Substituents
  • Ergoline skeleton
  • Indoloquinoline
  • Benzoquinoline
  • Pyrroloquinoline
  • 3-alkylindole
  • Indole
  • Indole or derivatives
  • Alkaloid or derivatives
  • Isoindole or derivatives
  • Aralkylamine
  • Benzenoid
  • Piperidine
  • Heteroaromatic compound
  • Pyrrole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Sulfenyl compound
  • Dialkylthioether
  • Azacycle
  • Thioether
  • Amine
  • Organosulfur compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point207.5°C
Boiling PointNot Available
Solubility5.84e-04 g/L
Predicted Properties
PropertyValueSource
Water Solubility0.00058 g/LALOGPS
logP4.17ALOGPS
logP4.23ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)17.35ChemAxon
pKa (Strongest Basic)9.49ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area19.03 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity97.02 m³·mol⁻¹ChemAxon
Polarizability38.4 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00mk-2790000000-1b8ba54d5d2568dccfc8Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0009000000-2ad79ab70c752608fcb3Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-066r-0679000000-884687417c70aa3885baSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0gbc-0910000000-9ab47ed0d8af7d82612bSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014i-0329000000-1f96cb9d349909c64088Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-066r-0965000000-a0878944c42cf3c2bb28Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-014i-0009000000-7411c2d1bd178ae44431Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-066r-0569000000-c11a58bee8ef4331cc99Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0gbc-0910000000-9ab47ed0d8af7d82612bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-1049000000-c6819e3f2395e229289aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014l-5193000000-1862aa31561fa2c8ca19Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9630000000-5bee80e04ab9297e67e1Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03dj-6059000000-275f5f6d9ede2d7e8a42Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-9044000000-e0318035317dbb8823a8Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-9110000000-89438865cc7ce104b644Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0009000000-ed1849c1b4a4c4ed7ddfSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-0009000000-d8500b18d37ff1636280Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03xr-6930000000-46296dfe5d34e43b2759Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0009000000-a594a3c3e856a1b44d62Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0009000000-b3447a9a81dcc08a70c5Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-07vi-1094000000-f4b2d4c92aa76ad840a9Spectrum
Toxicity Profile
Route of ExposureOral (16)
Mechanism of ToxicityThe 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. (2, 10, 11, 6, 7, 8)
MetabolismPergolide undergoes extensive first-pass hepatic metabolism and its metabolism are excreted mainly in the urine. (9) Route of Elimination: The major route of excretion is the kidney. Half Life: 27 hours
Toxicity ValuesLD50: 15 mg/kg (Oral, Rat) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesIndicated 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. (13, 16)
Minimum Risk LevelNot Available
Health EffectsIngestion 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. (5, 12)
SymptomsSymptoms 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. (14, 12)
TreatmentManagement 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. (15, 17)
Concentrations
Not Available
DrugBank IDDB01186
HMDB IDHMDB0015317
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkPergolide
Chemspider ID43503
ChEBI ID63617
PubChem Compound ID47811
Kegg Compound IDC07425
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

DrugSyn.org

MSDSLink
General References
1. Breitenstein C, Korsukewitz C, Floel A, Kretzschmar T, Diederich K, Knecht S: Tonic dopaminergic stimulation impairs associative learning in healthy subjects. Neuropsychopharmacology. 2006 Nov;31(11):2552-64. Epub 2006 Jul 26.
2. Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E: Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med. 2007 Jan 4;356(1):29-38.
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=11852289
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=15180134
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=16845152
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=18071034
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=2012117