Pergolide
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Identification
- Summary
Pergolide is a long-acting dopamine agonist that is uncommonly used for the management of Parkinson's disease, due to the risk for cardiac valvulopathy.
- Brand Names
- Permax
- Generic Name
- Pergolide
- DrugBank Accession Number
- DB01186
- Background
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 The drug was withdrawn from the US market in March 2007 and from the Canadian market in August 2007.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.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Vet approved, Withdrawn
- Structure
- Weight
- Average: 314.488
Monoisotopic: 314.181669532 - Chemical Formula
- C19H26N2S
- Synonyms
- Pergolida
- Pergolide
- Pergolidum
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 It was withdrawn from the US and Canadian markets in 2007 due to an increased risk of cardiac valvulopathy.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Parkinson's disease (pd) Regimen in combination with: Levodopa (DB01235), Carbidopa (DB00190) •••••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- 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.
Target Actions Organism AD(2) dopamine receptor agonistHumans AD(3) dopamine receptor agonistHumans AD(4) dopamine receptor agonistHumans AD(1B) dopamine receptor agonistHumans AD(1A) dopamine receptor agonistHumans U5-hydroxytryptamine receptor 1A agonistHumans U5-hydroxytryptamine receptor 2B agonistHumans U5-hydroxytryptamine receptor 2A agonistHumans U5-hydroxytryptamine receptor 1D agonistHumans UAlpha-2 adrenergic receptors agonistHumans U5-hydroxytryptamine receptor 1B agonistHumans U5-hydroxytryptamine receptor 2C agonistHumans UAlpha-1A adrenergic receptor agonistHumans UAlpha-1B adrenergic receptor agonistHumans UAlpha-1D adrenergic receptor agonistHumans - 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
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Oral, rat LD50: 15 mg/kg. Symptoms of overdose include nausea, vomiting, convulsions, decreased blood pressure, and CNS stimulation.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Pergolide is combined with 1,2-Benzodiazepine. Acebutolol The therapeutic efficacy of Pergolide can be decreased when used in combination with Acebutolol. Aceclofenac The risk or severity of hypertension can be increased when Pergolide is combined with Aceclofenac. Acemetacin The risk or severity of hypertension can be increased when Pergolide is combined with Acemetacin. Acenocoumarol The risk or severity of adverse effects can be increased when Pergolide is combined with Acenocoumarol. - Food Interactions
- Take with or without food.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Pergolide mesylate 55B9HQY616 66104-23-2 UWCVGPLTGZWHGS-ZORIOUSZSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Permax Tablet 1 mg/1 Oral Valeant Pharmaceuticals North America 2007-03-30 Not applicable US Permax Tablet 0.25 mg/1 Oral Valeant Pharmaceuticals North America 2007-03-30 Not applicable US Permax Tablet 0.05 mg/1 Oral Valeant Pharmaceuticals North America 2007-03-30 Not applicable US Permax Tab 0.05mg Tablet 0.05 mg Oral Eli Lilly & Co. Ltd. 1991-01-01 2000-08-03 Canada Permax Tab 0.25mg Tablet 0.25 mg Oral Eli Lilly & Co. Ltd. 1991-01-01 2000-08-03 Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Pergolide Mesylate Tablet 1 mg/1 Oral IVAX Pharmaceuticals, Inc. 2003-04-24 2009-02-28 US Pergolide Mesylate Tablet 1 mg/1 Oral Par Pharmaceutical 2002-11-27 2009-12-15 US Pergolide Mesylate Tablet 0.25 mg/1 Oral IVAX Pharmaceuticals, Inc. 2003-04-24 2009-02-28 US Pergolide Mesylate Tablet 0.05 mg/1 Oral Par Pharmaceutical 2002-11-27 2009-12-15 US Pergolide Mesylate Tablet 0.05 mg/1 Oral IVAX Pharmaceuticals, Inc. 2003-04-24 2009-02-28 US
Categories
- ATC Codes
- N04BC02 — Pergolide
- Drug Categories
- Adrenergic Agonists
- Adrenergic alpha-1 Receptor Agonists
- Adrenergic alpha-2 Receptor Agonists
- Adrenergic alpha-Agonists
- Agents producing tachycardia
- Agents that produce hypertension
- Alkaloids
- Anti-Parkinson Drugs
- Antidepressive Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Dopamine Agents
- Dopamine Agonists
- Ergolines
- Ergot Alkaloids and Derivatives
- Ergot-derivative Dopamine Receptor Agonists
- Ergot-derived Dopamine Receptor Agonist
- Heterocyclic Compounds, Fused-Ring
- Nervous System
- Neurotransmitter Agents
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT2 Receptor Agonists
- Serotonin Agents
- Serotonin Receptor Agonists
- Chemical TaxonomyProvided by Classyfire
- 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
- 3-alkylindole / Alkaloid or derivatives / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzoquinoline / Dialkylthioether / Ergoline skeleton show 17 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- organic heterotetracyclic compound, methyl sulfide, diamine (CHEBI:63617)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 24MJ822NZ9
- CAS number
- 66104-22-1
- 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[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),9,12,14-tetraene
- SMILES
- [H][C@@]12CC3=CNC4=CC=CC(=C34)[C@@]1([H])C[C@@H](CSC)CN2CCC
References
- Synthesis Reference
- US5034394
- General References
- 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. [Article]
- 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. [Article]
- FDA Approved Products: Permax (pergolide) [Link]
- External Links
- Human Metabolome Database
- HMDB0015317
- KEGG Compound
- C07425
- PubChem Compound
- 47811
- PubChem Substance
- 46507604
- ChemSpider
- 43503
- BindingDB
- 50028421
- 8047
- ChEBI
- 63617
- ChEMBL
- CHEMBL531
- ZINC
- ZINC000003786466
- Therapeutic Targets Database
- DAP000069
- PharmGKB
- PA450873
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Pergolide
- FDA label
- Download (204 KB)
- MSDS
- Download (76 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Basic Science Schizophrenia 1 somestatus stop reason just information to hide Not Available Completed Treatment Gilles de la Tourette's Syndrome 1 somestatus stop reason just information to hide Not Available No Longer Available Not Available Parkinson's Disease (PD) 1 somestatus stop reason just information to hide Not Available Suspended Not Available Cognitive Impairment (CI) / Negative Symptoms / Schizophrenia 1 somestatus stop reason just information to hide Not Available Unknown Status Diagnostic Other Personality Disorders / Schizotypal Personality Disorder 1 somestatus stop reason just information to hide
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
Form Route Strength Tablet Oral Tablet Oral 0.05 mg/1 Tablet Oral 0.25 mg/1 Tablet Oral 1 mg/1 Tablet Oral 0.05 mg Tablet Oral 0.25 mg Tablet Oral 1 mg - Prices
Unit description Cost Unit Pergolide mesylate 100% powder 1009.8USD g DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5114948 No 1992-05-19 2009-10-19 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 207.5 °C PhysProp logP 4 Not Available - Predicted Properties
Property Value Source Water Solubility 0.000584 mg/mL ALOGPS logP 4.17 ALOGPS logP 4.23 Chemaxon logS -5.7 ALOGPS pKa (Strongest Acidic) 17.35 Chemaxon pKa (Strongest Basic) 9.49 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 19.03 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 97.02 m3·mol-1 Chemaxon Polarizability 38.4 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9871 Caco-2 permeable + 0.5668 P-glycoprotein substrate Substrate 0.7201 P-glycoprotein inhibitor I Inhibitor 0.5589 P-glycoprotein inhibitor II Inhibitor 0.5145 Renal organic cation transporter Inhibitor 0.7757 CYP450 2C9 substrate Non-substrate 0.8671 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.5 CYP450 1A2 substrate Inhibitor 0.8932 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.5623 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6145 Ames test AMES toxic 0.751 Carcinogenicity Non-carcinogens 0.9694 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.8857 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.66 hERG inhibition (predictor II) Inhibitor 0.791
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 185.3472823 predictedDarkChem Lite v0.1.0 [M-H]- 185.9947823 predictedDarkChem Lite v0.1.0 [M-H]- 176.5673 predictedDeepCCS 1.0 (2019) [M+H]+ 186.4563823 predictedDarkChem Lite v0.1.0 [M+H]+ 187.1012823 predictedDarkChem Lite v0.1.0 [M+H]+ 178.96288 predictedDeepCCS 1.0 (2019) [M+Na]+ 185.4219823 predictedDarkChem Lite v0.1.0 [M+Na]+ 186.8716823 predictedDarkChem Lite v0.1.0 [M+Na]+ 185.24025 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (PubMed:21645528). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5 (By similarity)
- Specific Function
- dopamine binding
- Gene Name
- DRD2
- Uniprot ID
- P14416
- Uniprot Name
- D(2) dopamine receptor
- Molecular Weight
- 50618.91 Da
References
- 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. [Article]
- 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. [Article]
- Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [Article]
- Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [Article]
- 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. [Article]
- Mehta MA, Riedel WJ: Dopaminergic enhancement of cognitive function. Curr Pharm Des. 2006;12(20):2487-500. [Article]
- 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. [Article]
- FDA Approved Products: Permax (pergolide) [Link]
- NIH StatPearls: Dopamine agonists [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation
- Specific Function
- dopamine neurotransmitter receptor activity, coupled via Gi/Go
- Gene Name
- DRD3
- Uniprot ID
- P35462
- Uniprot Name
- D(3) dopamine receptor
- Molecular Weight
- 44194.315 Da
References
- Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [Article]
- Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General 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. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:9003072). Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:7512953, PubMed:7643093). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity)
- Specific Function
- dopamine binding
- Gene Name
- DRD4
- Uniprot ID
- P21917
- Uniprot Name
- D(4) dopamine receptor
- Molecular Weight
- 43900.84 Da
References
- Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [Article]
- Gilliland SL, Alper RH: Characterization of dopaminergic compounds at hD2short, hD4.2 and hD4.7 receptors in agonist-stimulated [35S]GTPgammaS binding assays. Naunyn Schmiedebergs Arch Pharmacol. 2000 May;361(5):498-504. doi: 10.1007/s002100000224. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase
- Specific Function
- dopamine binding
- Gene Name
- DRD5
- Uniprot ID
- P21918
- Uniprot Name
- D(1B) dopamine receptor
- Molecular Weight
- 52950.5 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase
- Specific Function
- arrestin family protein binding
- Gene Name
- DRD1
- Uniprot ID
- P21728
- Uniprot Name
- D(1A) dopamine receptor
- Molecular Weight
- 49292.765 Da
References
- Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [Article]
- Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [Article]
- FDA Approved Products: Permax (pergolide) [Link]
- NIH StatPearls: Dopamine agonists [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:37935376, PubMed:37935377, PubMed:8138923, PubMed:8393041). Also functions as a receptor for various drugs and psychoactive substances (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:38552625, PubMed:8138923, PubMed:8393041). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:8138923, PubMed:8393041). HTR1A is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission: signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores (PubMed:33762731, PubMed:35610220). Beta-arrestin family members regulate signaling by mediating both receptor desensitization and resensitization processes (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the response to anxiogenic stimuli (PubMed:18476671, PubMed:20363322, PubMed:20945968)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR1A
- Uniprot ID
- P08908
- Uniprot Name
- 5-hydroxytryptamine receptor 1A
- Molecular Weight
- 46106.335 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:18703043, PubMed:23519210, PubMed:7926008, PubMed:8078486, PubMed:8143856, PubMed:8882600). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances (PubMed:12970106, PubMed:18703043, PubMed:23519210, PubMed:23519215, PubMed:24357322, PubMed:28129538, PubMed:30127358, PubMed:36087581, PubMed:7926008, PubMed:8078486, PubMed:8143856). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:23519215, PubMed:28129538, PubMed:8078486, PubMed:8143856, PubMed:8882600). HTR2B is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:23519215, PubMed:28129538, PubMed:30127358, PubMed:36087581, PubMed:8078486, PubMed:8143856, PubMed:8882600). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:23519215, PubMed:28129538, PubMed:30127358, PubMed:36087581). 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 (By similarity). Plays a role in the regulation of behavior, including impulsive behavior (PubMed:21179162). Required for normal proliferation of embryonic cardiac myocytes and normal heart development (By similarity). Protects cardiomyocytes against apoptosis (By similarity). Plays a role in the adaptation of pulmonary arteries to chronic hypoxia (By similarity). Plays a role in vasoconstriction (By similarity). Required for normal osteoblast function and proliferation, and for maintaining normal bone density (By similarity). Required for normal proliferation of the interstitial cells of Cajal in the intestine (By similarity)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR2B
- Uniprot ID
- P41595
- Uniprot Name
- 5-hydroxytryptamine receptor 2B
- Molecular Weight
- 54297.41 Da
References
- 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. [Article]
- Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [Article]
- Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [Article]
- Hutcheson JD, Setola V, Roth BL, Merryman WD: Serotonin receptors and heart valve disease--it was meant 2B. Pharmacol Ther. 2011 Nov;132(2):146-57. doi: 10.1016/j.pharmthera.2011.03.008. Epub 2011 Apr 2. [Article]
- Gornemann T, Hubner H, Gmeiner P, Horowski R, Latte KP, Flieger M, Pertz HH: Characterization of the molecular fragment that is responsible for agonism of pergolide at serotonin 5-Hydroxytryptamine2B and 5-Hydroxytryptamine2A receptors. J Pharmacol Exp Ther. 2008 Mar;324(3):1136-45. doi: 10.1124/jpet.107.133165. Epub 2007 Dec 20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895, PubMed:21645528, PubMed:22300836, PubMed:35084960, PubMed:38552625). 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) (PubMed:28129538, PubMed:35084960). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:28129538, PubMed:35084960). HTR2A is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:28129538, PubMed:35084960). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538, PubMed:35084960). Affects neural activity, perception, cognition and mood (PubMed:18297054). 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 (By similarity)
- Specific Function
- 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding
- Gene Name
- HTR2A
- Uniprot ID
- P28223
- Uniprot Name
- 5-hydroxytryptamine receptor 2A
- Molecular Weight
- 52602.58 Da
References
- 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. [Article]
- Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [Article]
- Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [Article]
- Gornemann T, Hubner H, Gmeiner P, Horowski R, Latte KP, Flieger M, Pertz HH: Characterization of the molecular fragment that is responsible for agonism of pergolide at serotonin 5-Hydroxytryptamine2B and 5-Hydroxytryptamine2A receptors. J Pharmacol Exp Ther. 2008 Mar;324(3):1136-45. doi: 10.1124/jpet.107.133165. Epub 2007 Dec 20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:10452531, PubMed:1565658, PubMed:1652050, PubMed:33762731). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances (PubMed:10452531, PubMed:1565658, PubMed:1652050, PubMed:33762731). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:10452531, PubMed:1565658, PubMed:1652050, PubMed:33762731). HTR1D is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity (PubMed:33762731). Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity (PubMed:18476671, PubMed:20945968). May also play a role in regulating the release of other neurotransmitters (PubMed:18476671, PubMed:20945968). May play a role in vasoconstriction (PubMed:18476671, PubMed:20945968)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR1D
- Uniprot ID
- P28221
- Uniprot Name
- 5-hydroxytryptamine receptor 1D
- Molecular Weight
- 41906.38 Da
References
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General 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
- Specific Function
- alpha-1B adrenergic receptor binding
Components:
Name | UniProt ID |
---|---|
Alpha-2A adrenergic receptor | P08913 |
Alpha-2B adrenergic receptor | P18089 |
Alpha-2C adrenergic receptor | P18825 |
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:10452531, PubMed:1315531, PubMed:1328844, PubMed:1348246, PubMed:1351684, PubMed:1559993, PubMed:1565658, PubMed:1610347, PubMed:23519210, PubMed:23519215, PubMed:29925951, PubMed:8218242). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD) (PubMed:23519210, PubMed:23519215, PubMed:29925951). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:10452531, PubMed:1315531, PubMed:1328844, PubMed:1348246, PubMed:1351684, PubMed:1559993, PubMed:1565658, PubMed:1610347, PubMed:23519210, PubMed:23519215, PubMed:29925951, PubMed:8218242). HTR1B is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity (PubMed:29925951, PubMed:35610220). Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:29925951). Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior (PubMed:18476671, PubMed:20945968). Besides, plays a role in vasoconstriction of cerebral arteries (PubMed:15853772)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR1B
- Uniprot ID
- P28222
- Uniprot Name
- 5-hydroxytryptamine receptor 1B
- Molecular Weight
- 43567.535 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:12970106, PubMed:18703043, PubMed:19057895, PubMed:29398112, PubMed:7895773). 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) (PubMed:19057895, PubMed:29398112). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:18703043, PubMed:29398112). HTR2C is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:29398112). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:29398112). Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelanocortin neurons and the release of CRH that then regulates the release of corticosterone (By similarity). Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress (By similarity). Plays a role in insulin sensitivity and glucose homeostasis (By similarity)
- Specific Function
- 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding
- Gene Name
- HTR2C
- Uniprot ID
- P28335
- Uniprot Name
- 5-hydroxytryptamine receptor 2C
- Molecular Weight
- 51804.645 Da
References
- 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. [Article]
- Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [Article]
- Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- Curator comments
- Evidence regarding this target action is limited in the literature.
- General 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
- Specific Function
- alpha1-adrenergic receptor activity
- Gene Name
- ADRA1A
- Uniprot ID
- P35348
- Uniprot Name
- Alpha-1A adrenergic receptor
- Molecular Weight
- 51486.005 Da
References
- Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- Curator comments
- Evidence regarding this target action is limited in the literature.
- General 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
- Specific Function
- alpha1-adrenergic receptor activity
- Gene Name
- ADRA1B
- Uniprot ID
- P35368
- Uniprot Name
- Alpha-1B adrenergic receptor
- Molecular Weight
- 56835.375 Da
References
- Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- Curator comments
- Evidence regarding this target action is limited in the literature.
- General Function
- This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium
- Specific Function
- alpha1-adrenergic receptor activity
- Gene Name
- ADRA1D
- Uniprot ID
- P25100
- Uniprot Name
- Alpha-1D adrenergic receptor
- Molecular Weight
- 60462.205 Da
References
- Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Evidence regarding this enzyme action is limited in the literature.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at May 07, 2021 21:26