| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-06-23 18:06:59 |
| Primary Accession Number |
DB00248 |
| Secondary Accession Number |
|
| Name |
Cabergoline |
| Drug Type |
|
| 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 |
- Cabergolina [Spanish]
- Cabergolinum [Latin]
|
| Brand Names |
- Cabaser
- 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 |
 |
| 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  |
| KEGG Compound |
C08187  |
| PubChem Compound |
54746  |
| PubChem Substance |
10387  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA448708  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02242471  |
| RxList Link |
http://www.rxlist.com/cgi/generic/cabergoline.htm  |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Cabergoline  |
| 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 | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 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 |
|
| 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 |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| 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 |
- Wikipedia

- RxList

|
| Organisms Affected |
|
| Targets |
- D(2) dopamine receptor
|
|
Drug Target 1
[top]
|
| Target 1 ID |
831 |
| Target 1 Name |
D(2) dopamine receptor |
| Target 1 Synonyms |
- 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 |
|
| 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  |
| Target 1 UniProtKB/Swiss-Prot ID |
P14416  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
DRD2_HUMAN  |
| 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  |
| Target 1 GenAtlas ID |
DRD2  |
| Target 1 HGNC ID |
HGNC:3023  |
| Target 1 Chromosome Location |
11 |
| Target 1 Locus |
11q23 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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.
- 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 |
- 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
]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed
]
- 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
]
- 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
]
- 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
]
- 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
]
|