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Showing drug card for Cabergoline (DB00248)

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Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:59
Primary Accession Number DB00248
Secondary Accession Number
  • APRD00836
Name Cabergoline
Drug Type
  • Approved
  • Small Molecule
Description Cabergoline, a lysergic acid amide derivative, is a potent dopamine receptor agonist on D2 receptors. It also acts on dopamine receptors in lactophilic hypothalamus cells to suppress prolactin production in the pituitary gland. It is frequently used as a second-line agent in the management of prolactinomas when bromocriptine is ineffective. [Wikipedia]
Synonyms
  1. Cabergolina [Spanish]
  2. Cabergolinum [Latin]
Brand Names
  1. Cabaser
  2. Dostinex
Brand Mixtures Not Available
Chemical IUPAC Name N-[3-(Dimethylamino)propyl]-N-[(ethylamino)carbonyl]- 6-(2-propenyl)-8g-ergoline-8-carboxamide
Chemical Formula C26H37N5O2
Chemical Structure Structure
CAS Registry Number 81409-90-7
InChI Identifier InChI=1/C26H37N5O2/c1-5-11-30-17-19(25(32)31(26(33)27-6-2)13-8-12-29(3)4)14-21-20-9-7-10-22-24(20)18(16-28-22)15-23(21)30/h5,7,9-10,16,19,21,23,28H,1,6,8,11-15,17H2,2-4H3,(H,27,33)/t19-,21-,23-/m1/s1/f/h27H
InChI Key KORNTPPJEAJQIU-VXXMIMLHDS
KEGG Drug D00987 Link Image
KEGG Compound C08187 Link Image
PubChem Compound 54746 Link Image
PubChem Substance 10387 Link Image
ChEBI ID Not Available
PharmGKB ID PA448708 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02242471 Link Image
RxList Link http://www.rxlist.com/cgi/generic/cabergoline.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Cabergoline Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 451.6043
Monoisotopic Molecular Weight 451.2947
State Solid
Melting Point 102 - 104 oC
Experimental Water Solubility Insoluble Source: PhysProp
Predicted Water Solubility 6.40e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 2.6 Source: PhysProp
Predicted LogP 2.97 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.85 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CCNC(=O)N(CCCN(C)C)C(=O)[C@@H]1C[C@H]2[C@@H](CC3=CNC4=CC=CC2=C34)N(CC=C)C1
Canonical SMILES CCNC(=O)N(CCCN(C)C)C(=O)C1CC2C(CC3=CNC4=CC=CC2=C34)N(CC=C)C1
Drug Category
  • Antineoplastic Agents
  • Antiparkinson Agents
  • Dopamine Agonists
ATC Codes
AHFS Codes
  • 92:00.00
Indication For the treatment of hyperprolactinemic disorders, either idiopathic or due to pituitary adenomas.
Pharmacology Cabergoline is a dopamine receptor agonist and uncategorized drug which suppresses the production of prolactin in pituitary gland. It is an ergot-derivative. It has at times been used as an adjunct to SSRI antidepressants as there is some evidence that it counteracts certain side effects of those drugs such as reduced libido and anorgasmia. It also has been suggested online that it has a possible recreational use in reducing or eliminating the male refractory period.
Mechanism of Action The secretion of prolactin by the anterior pituitary is mainly under hypothalmic inhibitory control, likely exerted through release of dopamine by tuberoinfundibular neurons. Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D2 receptors. Results of in vitro studies demonstrate that cabergoline exerts a direct inhibitory effect on the secretion of prolactin by rat pituitary lactotrophs. Cabergoline decreased serum prolactin levels in reserpinized rats. Receptor-binding studies indicate that cabergoline has low affinity for dopamine D1, α1,- and α2- adrenergic, and 5-HT1- and 5-HT2-serotonin receptors.
Absorption First-pass effect is seen, however the absolute bioavailability is unknown.
Toxicity Overdosage might be expected to produce nasal congestion, syncope, or hallucinations.
Protein Binding Moderately bound (40% to 42%) to human plasma proteins in a concentration-independent manner.
Biotransformation Hepatic. Cabergoline is extensively metabolized, predominately via hydrolysis of the acylurea bond or the urea moiety. Cytochrome P-450 mediated metabolism appears to be minimal.
Half Life The elimination half-life is estimated from urinary data of 12 healthy subjects to range between 63 to 69 hours.
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Erythromycin Erythromycin increases serum levels and toxicity of cabergoline
Food Interactions
  • Absorption is not affected by food.
  • Take with food to improve tolerance.
Pathways Not Available
General References
  1. Wikipedia Link Image
  2. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. D(2) dopamine receptor
Drug Target 1 [top]
Target 1 ID 831
Target 1 Name D(2) dopamine receptor
Target 1 Synonyms
  1. Dopamine D2 receptor
Target 1 Gene Name DRD2
Target 1 Protein Sequence >D(2) dopamine receptor 
MDPLNLSWYDDDLERQNWSRPFNGSDGKADRPHYNYYATLLTLLIAVIVFGNVLVCMAVS
REKALQTTTNYLIVSLAVADLLVATLVMPWVVYLEVVGEWKFSRIHCDIFVTLDVMMCTA
SILNLCAISIDRYTAVAMPMLYNTRYSSKRRVTVMISIVWVLSFTISCPLLFGLNNADQN
ECIIANPAFVVYSSIVSFYVPFIVTLLVYIKIYIVLRRRRKRVNTKRSSRAFRAHLRAPL
KGNCTHPEDMKLCTVIMKSNGSFPVNRRRVEAARRAQELEMEMLSSTSPPERTRYSPIPP
SHHQLTLPDPSHHGLHSTPDSPAKPEKNGHAKDHPKIAKIFEIQTMPNGKTRTSLKTMSR
RKLSQQKEKKATQMLAIVLGVFIICWLPFFITHILNIHCDCNIPPVLYSAFTWLGYVNSA
VNPIIYTTFNIEFRKAFLKILHC
Target 1 Number of Residues 450
Target 1 Molecular Weight 50620
Target 1 Theoretical pI 9.85
Target 1 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
dopamine receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in dopamine receptor activity
Target 1 Specific Function This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 38-60
  • 72-97
  • 109-130
  • 152-174
  • 187-210
  • 374-397
  • 406-429
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 181432 Link Image
Target 1 UniProtKB/Swiss-Prot ID P14416 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name DRD2_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1332 bp 
ATGGATCCACTGAATCTGTCCTGGTATGATGATGATCTGGAGAGGCAGAACTGGAGCCGG
CCCTTCAACGGGTCAGACGGGAAGGCGGACAGACCCCACTACAACTACTATGCCACACTG
CTCACCCTGCTCATCGCTGTCATCGTCTTCGGCAACGTGCTGGTGTGCATGGCTGTGTCC
CGCGAGAAGGCGCTGCAGACCACCACCAACTACCTGATCGTCAGCCTCGCAGTGGCCGAC
CTCCTCGTCGCCACACTGGTCATGCCATGGGTTGTCTACCTGGAGGTGGTAGGTGAGTGG
AAATTCAGCAGGATTCACTGTGACATCTTCGTCACTCTGGACGTCATGATGTGCACGGCG
AGCATCCTGAACTTGTGTGCCATCAGCATCGACAGGTACACAGCTGTGGCCATGCCCATG
CTGTACAATACGCGCTACAGCTCCAAGCGCCGGGTCACCGTCATGATCTCCATCGTCTGG
GTCCTGTCCTTCACCATCTCCTGCCCACTCCTCTTCGGACTCAATAACGCAGACCAGAAC
GAGTGCATCATTGCCAACCCGGCCTTCGTGGTCTACTCCTCCATCGTCTCCTTCTACGTG
CCCTTCATTGTCACCCTGCTGGTCTACATCAAGATCTACATTGTCCTCCGCAGACGCCGC
AAGCGAGTCAACACCAAACGCAGCAGCCGAGCTTTCAGGGCCCACCTGAGGGCTCCACTA
AAGGGCAACTGTACTCACCCCGAGGACATGAAACTCTGCACCGTTATCATGAAGTCTAAT
GGGAGTTTCCCAGTGAACAGGCGGAGAGTGGAGGCTGCCCGGCGAGCCCAGGAGCTGGAG
ATGGAGATGCTCTCCAGCACCAGCCCACCCGAGAGGACCCGGTACAGCCCCATCCCACCC
AGCCACCACCAGCTGACTCTCCCCGACCCGTCCCACCACGGTCTCCACAGCACTCCTGAC
AGCCCCGCCAAACCAGAGAAGAATGGGCATGCCAAAGACCACCCCAAGATTGCCAAGATC
TTTGAGATCCAGACCATGCCCAATGGCAAAACCCGGACCTCCCTCAAGACCATGAGCCGT
AGAAAGCTCTCCCAGCAGAAGGAGAAGAAAGCCACTCAGATGCTCGCCATTGTTCTCGGC
GTGTTCATCATCTGCTGGCTGCCCTTCTTCATCACACACATCCTGAACATACACTGTGAC
TGCAACATCCCGCCTGTCCTGTACAGCGCCTTCACGTGGCTGGGCTATGTCAACAGCGCC
GTGAACCCCATCATCTACACCACCTTCAACATTGAGTTCCGCAAGGCCTTCCTGAAGATC
CTTCACTGCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID DRD2 Link Image
Target 1 GenAtlas ID DRD2 Link Image
Target 1 HGNC ID HGNC:3023 Link Image
Target 1 Chromosome Location 11
Target 1 Locus 11q23
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Klein C, Brin MF, Kramer P, Sena-Esteves M, de Leon D, Doheny D, Bressman S, Fahn S, Breakefield XO, Ozelius LJ: Association of a missense change in the D2 dopamine receptor with myoclonus dystonia. Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5173-6. [PubMed Link Image]
  2. Seeman P, Nam D, Ulpian C, Liu IS, Tallerico T: New dopamine receptor, D2(Longer), with unique TG splice site, in human brain. Brain Res Mol Brain Res. 2000 Mar 10;76(1):132-41. [PubMed Link Image]
  3. Araki K, Kuwano R, Morii K, Hayashi S, Minoshima S, Shimizu N, Katagiri T, Usui H, Kumanishi T, Takahashi Y: Structure and expression of human and rat D2 dopamine receptor genes. Neurochem Int. 1992 Jul;21(1):91-8. [PubMed Link Image]
  4. Dearry A, Falardeau P, Shores C, Caron MG: D2 dopamine receptors in the human retina: cloning of cDNA and localization of mRNA. Cell Mol Neurobiol. 1991 Oct;11(5):437-53. [PubMed Link Image]
  5. Stormann TM, Gdula DC, Weiner DM, Brann MR: Molecular cloning and expression of a dopamine D2 receptor from human retina. Mol Pharmacol. 1990 Jan;37(1):1-6. [PubMed Link Image]
  6. Robakis NK, Mohamadi M, Fu DY, Sambamurti K, Refolo LM: Human retina D2 receptor cDNAs have multiple polyadenylation sites and differ from a pituitary clone at the 5' non-coding region. Nucleic Acids Res. 1990 Mar 11;18(5):1299. [PubMed Link Image]
  7. Selbie LA, Hayes G, Shine J: DNA homology screening: isolation and characterization of the human D2A dopamine receptor subtype. Adv Second Messenger Phosphoprotein Res. 1990;24:9-14. [PubMed Link Image]
  8. Dal Toso R, Sommer B, Ewert M, Herb A, Pritchett DB, Bach A, Shivers BD, Seeburg PH: The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO J. 1989 Dec 20;8(13):4025-34. [PubMed Link Image]
  9. Grandy DK, Marchionni MA, Makam H, Stofko RE, Alfano M, Frothingham L, Fischer JB, Burke-Howie KJ, Bunzow JR, Server AC, et al.: Cloning of the cDNA and gene for a human D2 dopamine receptor. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9762-6. [PubMed Link Image]
  10. Selbie LA, Hayes G, Shine J: The major dopamine D2 receptor: molecular analysis of the human D2A subtype. DNA. 1989 Nov;8(9):683-9. [PubMed Link Image]
  11. 7902708 Itokawa M, Arinami T, Futamura N, Hamaguchi H, Toru M: A structural polymorphism of human dopamine D2 receptor, D2(Ser311-->Cys). Biochem Biophys Res Commun. 1993 Nov 15;196(3):1369-75.
  12. 8471125 Seeman P, Ohara K, Ulpian C, Seeman MV, Jellinger K, Van Tol HH, Niznik HB: Schizophrenia: normal sequence in the dopamine D2 receptor region that couples to G-proteins. DNA polymorphisms in D2. Neuropsychopharmacology. 1993 Feb;8(2):137-42.
Target 1 Drug References
  1. Ferone D, Pivonello R, Lastoria S, Faggiano A, Del Basso de Caro ML, Cappabianca P, Lombardi G, Colao A: In vivo and in vitro effects of octreotide, quinagolide and cabergoline in four hyperprolactinaemic acromegalics: correlation with somatostatin and dopamine D2 receptor scintigraphy. Clin Endocrinol (Oxf). 2001 Apr;54(4):469-77. [PubMed Link Image]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  3. Kageyama K, Nigawara T, Kamata Y, Takahashi T, Anzai J, Suzuki S, Osamura YR, Suda T: A case of macroprolactinoma with subclinical growth hormone production. Endocr J. 2002 Feb;49(1):41-7. [PubMed Link Image]
  4. Lombardi G, Varsaldi F, Miglio G, Papini MG, Battaglia A, Canonico PL: Cabergoline prevents necrotic neuronal death in an in vitro model of oxidative stress. Eur J Pharmacol. 2002 Dec 20;457(2-3):95-8. [PubMed Link Image]
  5. Saveanu A, Gunz G, Guillen S, Dufour H, Culler MD, Jaquet P: Somatostatin and dopamine-somatostatin multiple ligands directed towards somatostatin and dopamine receptors in pituitary adenomas. Neuroendocrinology. 2006;83(3-4):258-63. Epub 2006 Oct 13. [PubMed Link Image]
  6. Miyagi M, Arai N, Taya F, Itoh F, Komatsu Y, Kojima M, Isaji M: Effect of cabergoline, a long-acting dopamine D2 agonist, on reserpine-treated rodents. Biol Pharm Bull. 1996 Nov;19(11):1499-502. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.