Pergolide (T3D3011)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (17)XML
Targets (17)
Record Information
Version2.0
Creation Date2009-07-21 20:28:34 UTC
Update Date2014-12-24 20:25:55 UTC
Accession NumberT3D3011
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 The drug was withdrawn from the US market in March 2007 and from the Canadian market in August 2007.
Compound Type
  • Amine
  • Antidyskinetic
  • Antiparkinson Agent
  • Central Nervous System Agent
  • Dopamine Agonist
  • Drug
  • Ether
  • Metabolite
  • Neuroprotective Agent
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Pergolida
Pergolide Mesylate
Pergolide Methanesulfonate
Pergolidum
Permax
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[7.6.1.0²,⁷.0¹²,¹⁶]hexadeca-1(16),9,12,14-tetraene
Traditional Namepergolide
SMILES[H][C@]1(CSC)CN(CCC)[C@]2([H])CC3=CNC4=CC=CC(=C34)[C@@]2([H])C1
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 KeyInChIKey=YEHCICAEULNIGD-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
LogP4
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 RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00mk-2790000000-1b8ba54d5d2568dccfc82017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0009000000-2ad79ab70c752608fcb32017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-066r-0679000000-884687417c70aa3885ba2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0gbc-0910000000-9ab47ed0d8af7d82612b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014i-0329000000-1f96cb9d349909c640882017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-066r-0965000000-a0878944c42cf3c2bb282021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-014i-0009000000-7411c2d1bd178ae444312021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-066r-0569000000-c11a58bee8ef4331cc992021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0gbc-0910000000-9ab47ed0d8af7d82612b2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-1049000000-c6819e3f2395e229289a2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014l-5193000000-1862aa31561fa2c8ca192016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9630000000-5bee80e04ab9297e67e12016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03dj-6059000000-275f5f6d9ede2d7e8a422016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-9044000000-e0318035317dbb8823a82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-9110000000-89438865cc7ce104b6442016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0009000000-ed1849c1b4a4c4ed7ddf2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-0009000000-d8500b18d37ff16362802021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03xr-6930000000-46296dfe5d34e43b27592021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0009000000-a594a3c3e856a1b44d622021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0009000000-b3447a9a81dcc08a70c52021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-07vi-1094000000-f4b2d4c92aa76ad840a92021-10-11View Spectrum
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. (10, 11, 9, 5, 6, 7)
MetabolismPergolide undergoes extensive first-pass hepatic metabolism and its metabolism are excreted mainly in the urine. (8) 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. (4, 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)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01186
HMDB IDHMDB15317
PubChem Compound ID47811
ChEMBL IDCHEMBL531
ChemSpider ID43503
KEGG IDC07425
UniProt IDNot Available
OMIM ID
ChEBI ID63617
BioCyc IDNot Available
CTD IDNot Available
Stitch IDPergolide
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkPergolide
References
Synthesis Reference

DrugSyn.org

MSDSLink
General References
  1. 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. [18048412 ]
  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. [17202453 ]
  3. 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. [16880771 ]
  4. Richard JL: Some major mycotoxins and their mycotoxicoses--an overview. Int J Food Microbiol. 2007 Oct 20;119(1-2):3-10. Epub 2007 Jul 31. [17719115 ]
  5. Mantegani S, Brambilla E, Varasi M: Ergoline derivatives: receptor affinity and selectivity. Farmaco. 1999 May 30;54(5):288-96. [10418123 ]
  6. Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
  7. 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. [16982285 ]
  8. Blin O: The pharmacokinetics of pergolide in Parkinson's disease. Curr Opin Neurol. 2003 Dec;16 Suppl 1:S9-12. [15180132 ]
  9. Jenner P: Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson's disease. Curr Opin Neurol. 2003 Dec;16 Suppl 1:S3-7. [15180131 ]
  10. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  11. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
  12. Drugs.com [Link]
  13. Wikipedia. Ergoline. Last Updated 2 April 2010. [Link]
  14. Wikipedia. Ergotism. Last Updated 6 April 2010. [Link]
  15. Van den Enden, E. (2004). Illustrated Lecture Notes on Tropical Medicine. [Link]
  16. Wikipedia. Pergolide. Last Updated 15 March 2010. [Link]
  17. RxList: The Internet Drug Index (2010). Permax (Pergolide). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. D(2) dopamine receptor
General Function:
Potassium channel regulator activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular Weight:
50618.91 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.004 uMNot AvailableBindingDB 50017543
Inhibitory0.05 uMNot AvailableBindingDB 50017543
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Huettl P, Gerhardt GA, Browning MD, Masserano JM: Effects of dopamine receptor agonists and antagonists on catecholamine release in bovine chromaffin cells. J Pharmacol Exp Ther. 1991 May;257(2):567-74. [1674528 ]
  3. Linazasoro G, Obeso JA, Gomez JC, Martinez M, Antonini A, Leenders KL: Modification of dopamine D2 receptor activity by pergolide in Parkinson's disease: an in vivo study by PET. Clin Neuropharmacol. 1999 Sep-Oct;22(5):277-80. [10516878 ]
  4. Fuller RW, Hemrick-Luecke SK, Perry KW, Toomey RE: Pergolide elevation of MHPG sulphate concentration in rat hypothalamus blocked by spiperone and mimicked by other dopamine agonists. J Pharm Pharmacol. 1985 Apr;37(4):268-70. [2860228 ]
  5. Paturle L, Fage D, Fourrier O, Vernier P, Feuerstein C, Demenge P, Scatton B: Cortical ablation fails to influence striatal dopamine target cell supersensitivity induced by nigrostriatal denervation in the rat. Brain Res. 1987 Feb 3;402(2):383-6. [3828803 ]
  6. Mehta MA, Riedel WJ: Dopaminergic enhancement of cognitive function. Curr Pharm Des. 2006;12(20):2487-500. [16842172 ]
  7. Jenner P: Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson's disease. Curr Opin Neurol. 2003 Dec;16 Suppl 1:S3-7. [15180131 ]
  8. Heier RF, Dolak LA, Duncan JN, Hyslop DK, Lipton MF, Martin IJ, Mauragis MA, Piercey MF, Nichols NF, Schreur PJ, Smith MW, Moon MW: Synthesis and biological activities of (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and its metabolites. J Med Chem. 1997 Feb 28;40(5):639-46. [9057850 ]
  9. Wilcox RE, Tseng T, Brusniak MY, Ginsburg B, Pearlman RS, Teeter M, DuRand C, Starr S, Neve KA: CoMFA-based prediction of agonist affinities at recombinant D1 vs D2 dopamine receptors. J Med Chem. 1998 Oct 22;41(22):4385-99. [9784114 ]
Target Details
2. 5-hydroxytryptamine receptor 1A
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular Weight:
46106.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0018 uMNot AvailableBindingDB 50017543
Inhibitory0.004 uMNot AvailableBindingDB 50017543
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  3. Chidester CG, Lin CH, Lahti RA, Haadsma-Svensson SR, Smith MW: Comparison of 5-HT1A and dopamine D2 pharmacophores. X-ray structures and affinities of conformationally constrained ligands. J Med Chem. 1993 May 14;36(10):1301-15. [8496900 ]
  4. Heier RF, Dolak LA, Duncan JN, Hyslop DK, Lipton MF, Martin IJ, Mauragis MA, Piercey MF, Nichols NF, Schreur PJ, Smith MW, Moon MW: Synthesis and biological activities of (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and its metabolites. J Med Chem. 1997 Feb 28;40(5):639-46. [9057850 ]
Target Details
3. D(3) dopamine receptor
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name:
DRD3
Uniprot ID:
P35462
Molecular Weight:
44224.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.004 uMNot AvailableBindingDB 50017543
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  3. Wachtel H: Antiparkinsonian dopamine agonists: a review of the pharmacokinetics and neuropharmacology in animals and humans. J Neural Transm Park Dis Dement Sect. 1991;3(3):151-201. [1683537 ]
  4. Heier RF, Dolak LA, Duncan JN, Hyslop DK, Lipton MF, Martin IJ, Mauragis MA, Piercey MF, Nichols NF, Schreur PJ, Smith MW, Moon MW: Synthesis and biological activities of (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and its metabolites. J Med Chem. 1997 Feb 28;40(5):639-46. [9057850 ]
Target Details
4. 5-hydroxytryptamine receptor 2A
General Function:
Virus receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular Weight:
52602.58 Da
References
  1. Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I: Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. Eur J Pharmacol. 2008 Oct 10;594(1-3):32-8. doi: 10.1016/j.ejphar.2008.07.040. Epub 2008 Jul 30. [18703043 ]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
Target Details
5. 5-hydroxytryptamine receptor 2C
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular Weight:
51820.705 Da
References
  1. Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I: Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. Eur J Pharmacol. 2008 Oct 10;594(1-3):32-8. doi: 10.1016/j.ejphar.2008.07.040. Epub 2008 Jul 30. [18703043 ]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
Target Details
6. D(1A) dopamine receptor
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular Weight:
49292.765 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2.02 uMNot AvailableBindingDB 50017543
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Jenner P: Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson's disease. Curr Opin Neurol. 2003 Dec;16 Suppl 1:S3-7. [15180131 ]
  3. Wilcox RE, Tseng T, Brusniak MY, Ginsburg B, Pearlman RS, Teeter M, DuRand C, Starr S, Neve KA: CoMFA-based prediction of agonist affinities at recombinant D1 vs D2 dopamine receptors. J Med Chem. 1998 Oct 22;41(22):4385-99. [9784114 ]
Target Details
7. 5-hydroxytryptamine receptor 1D
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.
Gene Name:
HTR1D
Uniprot ID:
P28221
Molecular Weight:
41906.38 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
Target Details
8. Alpha-2A adrenergic receptor
General Function:
Thioesterase binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
Target Details
9. Alpha-2B adrenergic receptor
General Function:
Epinephrine binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
Target Details
10. Alpha-2C adrenergic receptor
General Function:
Protein homodimerization activity
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name:
ADRA2C
Uniprot ID:
P18825
Molecular Weight:
49521.585 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
Target Details
11. 5-hydroxytryptamine receptor 1B
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
Gene Name:
HTR1B
Uniprot ID:
P28222
Molecular Weight:
43567.535 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
Target Details
12. 5-hydroxytryptamine receptor 2B
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine.
Gene Name:
HTR2B
Uniprot ID:
P41595
Molecular Weight:
54297.41 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
Target Details
13. Alpha-1A adrenergic receptor
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
Target Details
14. Alpha-1B adrenergic receptor
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
Target Details
15. Alpha-1D adrenergic receptor
General Function:
Alpha1-adrenergic receptor activity
Specific Function:
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name:
ADRA1D
Uniprot ID:
P25100
Molecular Weight:
60462.205 Da
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
Target Details
16. D(1B) dopamine receptor
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD5
Uniprot ID:
P21918
Molecular Weight:
52950.5 Da
References
  1. Jenner P: Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson's disease. Curr Opin Neurol. 2003 Dec;16 Suppl 1:S3-7. [15180131 ]
Target Details
17. D(4) dopamine receptor
General Function:
Sh3 domain binding
Specific Function:
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).
Gene Name:
DRD4
Uniprot ID:
P21917
Molecular Weight:
48359.86 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]