Identification

Name
Pergolide
Accession Number
DB01186  (APRD00663)
Type
Small Molecule
Groups
Approved, Investigational, Vet approved, Withdrawn
Description

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 The drug was withdrawn from the US market in March 2007 and from the Canadian market in August 2007.

Structure
Thumb
Synonyms
  • Pergolida
  • Pergolidum
Product Ingredients
IngredientUNIICASInChI Key
Pergolide mesylate55B9HQY61666104-23-2UWCVGPLTGZWHGS-ZORIOUSZSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Permax Tab 0.05mgTablet0.05 mgOralEli Lilly & Co. Ltd.1991-01-012000-08-03Canada
Permax Tab 0.25mgTablet0.25 mgOralEli Lilly & Co. Ltd.1991-01-012000-08-03Canada
Permax Tab 1mgTablet1 mgOralEli Lilly & Co. Ltd.1991-01-012000-08-03Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pergolide MesylateTablet0.05 mg/1OralIVAX Pharmaceuticals, Inc.2003-04-242009-02-28Us
Pergolide MesylateTablet0.25 mg/1OralPar Pharmaceutical2002-11-272009-12-15Us
Pergolide MesylateTablet1 mg/1OralIVAX Pharmaceuticals, Inc.2003-04-242009-02-28Us
Pergolide MesylateTablet1 mg/1OralPar Pharmaceutical2002-11-272009-12-15Us
Pergolide MesylateTablet0.25 mg/1OralIVAX Pharmaceuticals, Inc.2003-04-242009-02-28Us
Pergolide MesylateTablet0.05 mg/1OralPar Pharmaceutical2002-11-272009-12-15Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
PermaxPergolide (0.05 mg/1)TabletOralValeant Pharmaceuticals, Inc.2007-03-30Not applicableUs
PermaxPergolide (1 mg/1)TabletOralValeant Pharmaceuticals, Inc.2007-03-30Not applicableUs
PermaxPergolide (0.25 mg/1)TabletOralValeant Pharmaceuticals, Inc.2007-03-30Not applicableUs
International/Other Brands
Permax (Eli Lilly)
Categories
UNII
24MJ822NZ9
CAS number
66104-22-1
Weight
Average: 314.488
Monoisotopic: 314.181669532
Chemical Formula
C19H26N2S
InChI Key
YEHCICAEULNIGD-MZMPZRCHSA-N
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
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
SMILES
[H][C@@]12CC3=CNC4=CC=CC(=C34)[C@@]1([H])C[C@@H](CSC)CN2CCC

Pharmacology

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.

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.

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.

TargetActionsOrganism
AD(2) dopamine receptor
agonist
Human
AD(3) dopamine receptor
agonist
Human
UD(4) dopamine receptor
agonist
Human
U5-hydroxytryptamine receptor 1A
agonist
Human
U5-hydroxytryptamine receptor 2B
agonist
Human
U5-hydroxytryptamine receptor 2A
agonist
Human
U5-hydroxytryptamine receptor 1D
agonist
Human
UAlpha-2B adrenergic receptor
agonist
Human
UAlpha-2A adrenergic receptor
agonist
Human
UAlpha-2C adrenergic receptor
agonist
Human
UD(1B) dopamine receptor
agonist
Human
UD(1A) dopamine receptor
agonist
Human
U5-hydroxytryptamine receptor 1B
agonist
Human
U5-hydroxytryptamine receptor 2C
agonist
Human
UAlpha-1A adrenergic receptor
agonist
Human
UAlpha-1B adrenergic receptor
agonist
Human
UAlpha-1D adrenergic receptor
agonist
Human
Absorption

Significant amount may be absorbed (evidence on bioavailability still lacking).

Volume of distribution
Not Available
Protein binding

90%

Metabolism

Extensively hepatic.

Route of elimination

The major route of excretion is the kidney.

Half life

27 hours

Clearance
Not Available
Toxicity

Oral, rat LD50: 15 mg/kg. Symptoms of overdose include nausea, vomiting, convulsions, decreased blood pressure, and CNS stimulation.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
4-MethoxyamphetaminePergolide may increase the hypertensive activities of 4-Methoxyamphetamine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe metabolism of Pergolide can be decreased when combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AcebutololThe therapeutic efficacy of Pergolide can be decreased when used in combination with Acebutolol.
AcepromazineAcepromazine may decrease the vasoconstricting activities of Pergolide.
AcetazolamideThe risk or severity of adverse effects can be increased when Pergolide is combined with Acetazolamide.
Acetyl sulfisoxazoleThe risk or severity of adverse effects can be increased when Pergolide is combined with Acetyl sulfisoxazole.
AgmatinePergolide may increase the hypertensive and vasoconstricting activities of Agmatine.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Pergolide.
AlfuzosinThe therapeutic efficacy of Pergolide can be decreased when used in combination with Alfuzosin.
AlimemazineThe risk or severity of adverse effects can be increased when Alimemazine is combined with Pergolide.
Food Interactions
  • Take with food to reduce gastric irritation and nausea

References

Synthesis Reference
US5034394
General References
  1. 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. [PubMed:17202453]
  2. 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. [PubMed:16880771]
External Links
Human Metabolome Database
HMDB0015317
KEGG Compound
C07425
PubChem Compound
47811
PubChem Substance
46507604
ChemSpider
43503
BindingDB
50017543
ChEBI
63617
ChEMBL
CHEMBL531
Therapeutic Targets Database
DAP000069
PharmGKB
PA450873
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pergolide
ATC Codes
N04BC02 — Pergolide
FDA label
Download (204 KB)
MSDS
Download (76 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentCocaine-Related Disorders1
2CompletedTreatmentCocaine-Related Disorders / Substance-Related Disorders1
2SuspendedNot AvailableCognitive Impairments / Negative Symptoms / Schizophrenic Disorders1
3CompletedTreatmentCocaine-Related Disorders1
3CompletedTreatmentIdiopathic Parkinson's Disease1
Not AvailableCompletedBasic ScienceSchizophrenic Disorders1
Not AvailableCompletedTreatmentGilles de la Tourette's Syndrome1
Not AvailableNo Longer AvailableNot AvailableParkinson's Disease (PD)1
Not AvailableUnknown StatusDiagnosticOther Personality Disorders / Schizotypal Personality Disorder1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Amarin Pharmaceuticals
  • Institutional Maintenance Supply
  • Legacy Pharmaceuticals Packaging LLC
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Par Pharmaceuticals
  • Pharmaceutical Utilization Management Program VA Inc.
  • Teva Pharmaceutical Industries Ltd.
  • Valeant Ltd.
Dosage forms
FormRouteStrength
TabletOral0.05 mg/1
TabletOral0.25 mg/1
TabletOral1 mg/1
TabletOral0.05 mg
TabletOral0.25 mg
TabletOral1 mg
Prices
Unit descriptionCostUnit
Pergolide mesylate 100% powder1009.8USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5114948No1992-10-192009-10-19Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)207.5 °CPhysProp
logP4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000584 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity97.02 m3·mol-1ChemAxon
Polarizability38.4 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9871
Caco-2 permeable+0.5668
P-glycoprotein substrateSubstrate0.7201
P-glycoprotein inhibitor IInhibitor0.5589
P-glycoprotein inhibitor IIInhibitor0.5145
Renal organic cation transporterInhibitor0.7757
CYP450 2C9 substrateNon-substrate0.8671
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateInhibitor0.8932
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.5623
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6145
Ames testAMES toxic0.751
CarcinogenicityNon-carcinogens0.9694
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8857 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.66
hERG inhibition (predictor II)Inhibitor0.791
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0009000000-2ad79ab70c752608fcb3
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-066r-0679000000-884687417c70aa3885ba
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0gbc-0910000000-9ab47ed0d8af7d82612b
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0329000000-1f96cb9d349909c64088

Taxonomy

Description
This compound belongs to the class of organic compounds known as indoloquinolines. These are polycyclic aromatic compounds containing an indole fused to a quinoline.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Indoloquinolines
Direct Parent
Indoloquinolines
Alternative Parents
Ergoline and derivatives / Benzoquinolines / Pyrroloquinolines / 3-alkylindoles / Isoindoles and derivatives / Aralkylamines / Benzenoids / Piperidines / Pyrroles / Heteroaromatic compounds
show 6 more
Substituents
Ergoline skeleton / Indoloquinoline / Benzoquinoline / Pyrroloquinoline / 3-alkylindole / Indole / Indole or derivatives / Alkaloid or derivatives / Isoindole or derivatives / Aralkylamine
show 17 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organic heterotetracyclic compound, methyl sulfide, diamine (CHEBI:63617)

Targets

Details
1. D(2) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. 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. [PubMed:2860228]
  3. 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. [PubMed:1674528]
  4. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  5. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
  6. 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. [PubMed:10516878]
  7. Mehta MA, Riedel WJ: Dopaminergic enhancement of cognitive function. Curr Pharm Des. 2006;12(20):2487-500. [PubMed:16842172]
  8. 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. [PubMed:3828803]
Details
2. D(3) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44224.335 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. [PubMed:18691132]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed: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. [PubMed:1683537]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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 ...
Gene Name
DRD4
Uniprot ID
P21917
Uniprot Name
D(4) dopamine receptor
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. [PubMed:18691132]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 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. [PubMed:18691132]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 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. [PubMed: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. [PubMed:18691132]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
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. [PubMed: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. [PubMed:18691132]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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 subst...
Gene Name
HTR1D
Uniprot ID
P28221
Uniprot Name
5-hydroxytryptamine receptor 1D
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. [PubMed:18691132]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
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. [PubMed:18691132]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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 oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
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. [PubMed:18691132]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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
Uniprot Name
Alpha-2C adrenergic receptor
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. [PubMed:18691132]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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
Uniprot Name
D(1B) dopamine receptor
Molecular Weight
52950.5 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. [PubMed:18691132]
Details
12. D(1A) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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 subst...
Gene Name
HTR1B
Uniprot ID
P28222
Uniprot Name
5-hydroxytryptamine receptor 1B
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. [PubMed:18691132]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
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. [PubMed: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. [PubMed:18691132]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 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. [PubMed:18691132]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Wynalda MA, Wienkers LC: Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab Dispos. 1997 Oct;25(10):1211-4. [PubMed:9321526]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 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. [PubMed:18691132]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on September 13, 2018 15:49