CABERGOLINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H37N5O2
Molecular Weight	451.6043
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC3=CNC4=C3C(=CC=C4)[C@@]1([H])C[C@H](CN2CC=C)C(=O)N(CCCN(C)C)C(=O)NCC

InChI

InChIKey=KORNTPPJEAJQIU-KJXAQDMKSA-N

InChI=1S/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

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2008/078035Orig1s000.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/dosage/cabergoline.html http://www.wikidoc.org/index.php/Cabergoline http://www.rxlist.com/dostinex-drug.htm

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. It is FDA approved for the treatment of hyperprolactinemic disorders, either idiopathic or due to pituitary adenomas. Common adverse reactions include constipation, nausea, dizziness, headache and fatigue. Cabergoline should not be administered concurrently with D-antagonists, such as phenothiazines, butyrophenones, thioxanthenes, or metoclopramide.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D3 receptor 89 Target ID: CHEMBL234 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18691132	Agonist 2637	1.5 nM [Ki]
Dopamine receptors; D2 & D3 3 Target ID: CHEMBL2095169 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18691132	Agonist 2637	0.5 nM [Ki]
Serotonin 2b (5-HT2b) receptor 60 Target ID: CHEMBL1833 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18691132	Agonist 2637	1.2 nM [Ki]
Dopamine D2 receptor 290 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8951172 http://www.drugbank.ca/drugs/DB00248	Agonist 2637	0.69 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperprolactinemic disorders, idiopathic 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2008/078035Orig1s000.pdf	Primary		Approved 8307	CABERGOLINE Approved Use Cabergoline tablets are indicated for the treatment of hyperprolactinemic disorders, either idiopathic or due to pituitary adenomas. Launch Date 1.13581438E12
Hyperprolactinemic disorders, due to pituitary adenomas 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2008/078035Orig1s000.pdf	Primary		Approved 8307	CABERGOLINE Approved Use Cabergoline tablets are indicated for the treatment of hyperprolactinemic disorders, either idiopathic or due to pituitary adenomas. Launch Date 1.13581438E12

C_max

Value	Dose	Analyte	Population
33.3 ng/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7883840	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered:	CABERGOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
40.3 ng/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7883840	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	CABERGOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
67 ng/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7883840	1.5 mg single, oral dose: 1.5 mg route of administration: Oral experiment type: SINGLE co-administered:	CABERGOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
12952 ng × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7883840	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered:	CABERGOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1884 ng × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7883840	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	CABERGOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2546 ng × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7883840	1.5 mg single, oral dose: 1.5 mg route of administration: Oral experiment type: SINGLE co-administered:	CABERGOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
68.54 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7884663	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		CABERGOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
60% REVIEW https://pubmed.ncbi.nlm.nih.gov/12844325	unknown, unknown		CABERGOLINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
20 mg 1 times / day multiple, oral Highest studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Co-administed with:: L-dopa, po(370.6 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/16367894 Page: p.18, p.19, p.22	unhealthy, 41.0–73.5 n = 34 Health Status: unhealthy Condition: Parkinson’s disease Age Group: 41.0–73.5 Sex: M+F Population Size: 34 Sources: https://pubmed.ncbi.nlm.nih.gov/16367894 Page: p.18, p.19, p.22	Sources: https://pubmed.ncbi.nlm.nih.gov/16367894 Page: p.18, p.19, p.22
2 mg 1 times / day multiple, oral (min) Overdose Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4	unhealthy Health Status: unhealthy Condition: Parkinson’s disease Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4	Other AEs: Cardiac valvulopathy... Other AEs: Cardiac valvulopathy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4
0.5 mg 2 times / week multiple, oral Recommended Dose: 0.5 mg, 2 times / week Route: oral Route: multiple Dose: 0.5 mg, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.9	unhealthy n = 221 Health Status: unhealthy Condition: Hyperprolactinemic disorders Population Size: 221 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.9	Disc. AE: Headache, Nausea... AEs leading to discontinuation/dose reduction: Headache (1.4%) Nausea (0.9%) Vomiting (0.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.9
1 mg 2 times / week multiple, oral (max) Recommended Dose: 1 mg, 2 times / week Route: oral Route: multiple Dose: 1 mg, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4	unhealthy Health Status: unhealthy Condition: Hyperprolactinemic disorders Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4	Disc. AE: Pleural effusion, Pulmonary fibrosis... Other AEs: Cardiac valvulopathy, Pericardial fibrosis... AEs leading to discontinuation/dose reduction: Pleural effusion Pulmonary fibrosis Other AEs: Cardiac valvulopathy Pericardial fibrosis Retroperitoneal fibrosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4

AEs

AE	Significance	Dose	Population
Cardiac valvulopathy		2 mg 1 times / day multiple, oral (min) Overdose Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4	unhealthy Health Status: unhealthy Condition: Parkinson’s disease Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4
Nausea	0.9% Disc. AE	0.5 mg 2 times / week multiple, oral Recommended Dose: 0.5 mg, 2 times / week Route: oral Route: multiple Dose: 0.5 mg, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.9	unhealthy n = 221 Health Status: unhealthy Condition: Hyperprolactinemic disorders Population Size: 221 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.9
Vomiting	0.9% Disc. AE	0.5 mg 2 times / week multiple, oral Recommended Dose: 0.5 mg, 2 times / week Route: oral Route: multiple Dose: 0.5 mg, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.9	unhealthy n = 221 Health Status: unhealthy Condition: Hyperprolactinemic disorders Population Size: 221 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.9
Headache	1.4% Disc. AE	0.5 mg 2 times / week multiple, oral Recommended Dose: 0.5 mg, 2 times / week Route: oral Route: multiple Dose: 0.5 mg, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.9	unhealthy n = 221 Health Status: unhealthy Condition: Hyperprolactinemic disorders Population Size: 221 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.9
Cardiac valvulopathy		1 mg 2 times / week multiple, oral (max) Recommended Dose: 1 mg, 2 times / week Route: oral Route: multiple Dose: 1 mg, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4	unhealthy Health Status: unhealthy Condition: Hyperprolactinemic disorders Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4
Pericardial fibrosis		1 mg 2 times / week multiple, oral (max) Recommended Dose: 1 mg, 2 times / week Route: oral Route: multiple Dose: 1 mg, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4	unhealthy Health Status: unhealthy Condition: Hyperprolactinemic disorders Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4
Retroperitoneal fibrosis		1 mg 2 times / week multiple, oral (max) Recommended Dose: 1 mg, 2 times / week Route: oral Route: multiple Dose: 1 mg, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4	unhealthy Health Status: unhealthy Condition: Hyperprolactinemic disorders Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4
Pleural effusion	Disc. AE	1 mg 2 times / week multiple, oral (max) Recommended Dose: 1 mg, 2 times / week Route: oral Route: multiple Dose: 1 mg, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4	unhealthy Health Status: unhealthy Condition: Hyperprolactinemic disorders Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4
Pulmonary fibrosis	Disc. AE	1 mg 2 times / week multiple, oral (max) Recommended Dose: 1 mg, 2 times / week Route: oral Route: multiple Dose: 1 mg, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4	unhealthy Health Status: unhealthy Condition: Hyperprolactinemic disorders Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020664s011lbl.pdf Page: p.4

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1401

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/31183987/ Page: -	likely

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1670	substrate 3264 Sources: https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1016/j.clpt.2004.12.204 Page: -	yes		yes (co-administration study) Comment: n healthy male volunteers, the mean of Cmax and AUC of cabergoline increased around 2.7 times by coadministration of clarithromycin. Sources: https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1016/j.clpt.2004.12.204 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3286	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3286
ChemicalBook	CB0282495	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0282495
MolPort	MolPort-003-845-557	https://www.molport.com/shop/molecule-link/MolPort-003-845-557
ZINC	ZINC000003800008	http://zinc15.docking.org/substances/ZINC000003800008
eMolecules	2727031	https://www.emolecules.com/cgi-bin/more?vid=2727031

PubMed

Title	Date	PubMed
Use of the dopamine agonists bromocriptine and cabergoline in the management of risperidone-induced hyperprolactinemia in patients with psychotic disorders.	2000 Dec	11194712
Bait-delivered cabergoline for the reproductive control of the red fox (Vulpes vulpes): estimating mammalian non-target risk in south-eastern Australia.	2001	11999299
Actigraph analysis of diurnal motor fluctuations during dopamine agonist therapy.	2001	11741098
Regulation of dopamine receptors and motor behavior following pulsatile and continuous dopaminergic replacement strategies in the MPTP primate model.	2001	11553994
Cabergoline versus bromocriptine for levodopa-induced complications in Parkinson's disease.	2001	11279721
A study of excessive daytime sleepiness and its clinical significance in three groups of Parkinson's disease patients taking pramipexole, cabergoline and levodopa mono and combination therapy.	2001	11261748
Minor tumour shrinkage in nonfunctioning pituitary adenomas by long-term treatment with the dopamine agonist cabergoline.	2001 Aug	12138990
Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats.	2001 Aug	11473532
Control of red fox (Vulpes vulpes) fertility with cabergoline: dose response and timing of intervention.	2001 Jul	11425339
Laboratory and clinical experience in 55 patients with macroprolactinemia identified by a simple polyethylene glycol precipitation method.	2001 Jun	11397880
Cabergoline-induced CSF rhinorrhea in patients with macroprolactinoma. Report of three cases.	2001 Mar	11314748
Sudden daytime sleep onset in Parkinson's disease: polysomnographic recordings.	2001 May	11391745
Study of the change of prolactin and progesterone during dopaminergic agonist treatments in pseudopregnant bitches.	2001 May 31	11348786
Effectiveness of cabergoline for termination of pregnancy in silver fox (Vulpes vulpes fulva).	2001 Oct	11885743
Determination of cabergoline by electrospray ionization tandem mass spectrometry: picogram detection via column focusing sample introduction.	2001 Oct 15	11681474
Comparison of the effects of cabergoline and bromocriptine on prolactin levels in hyperprolactinemic patients.	2001 Sep	11579944
Disorders of prolactin secretion.	2001 Sep	11571932
Medical management of prolactin-secreting pituitary adenomas.	2002	12675502
Assessment of cabergoline as a reproductive inhibitor in coyotes (Canis latrans).	2002	12220164
DA agonists -- ergot derivatives: bromocriptine: management of Parkinson's disease.	2002	12211141
Control of fertility in the red fox (Vulpes vulpes): effect of a single oral dose of cabergoline in early pregnancy.	2002	12051520
Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease.	2002	11978145
Pregnancy termination in the bitch and queen.	2002 Aug	12476814
Switch to quetiapine in antipsychotic agent-related hyperprolactinemia.	2002 Dec	12522680
Alopecia induced by dopamine agonists.	2002 Dec 24	12499512
Macroprolactinoma associated with Cushing's disease, successfully treated with cabergoline.	2002 Feb	11929090
Treatment of Parkinson's disease and restless legs syndrome with cabergoline, a long-acting dopamine agonist.	2002 Jul-Aug	12166546
Use of cabergoline to treat primary and secondary anestrus in dogs.	2002 Jun 1	12051504
Cabergoline can increase penile erections and libido.	2002 Mar 12	11889258
Hyperprolactinemia: etiology, diagnosis, and management.	2002 Nov	12536359
Cabergoline plasma concentration is increased during concomitant treatment with itraconazole.	2002 Nov	12465083
Long term tolerability of high dose ergoline derived dopamine agonist therapy for the treatment of Parkinson's disease.	2002 Nov	12397168
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor.	2002 Nov	12388667
Detecting dose-response using contrasts: asymptotic power and sample size determination for binomial data.	2002 Nov 30	12407675
Autonomic failure mimicing dopamine agonist induced vertigo in a patient with macroprolactinoma.	2002 Oct	12397537
A practical synthesis of cabergoline.	2002 Oct 4	12354014
Combination of two different dopamine agonists in the management of Parkinson's disease.	2002 Sep	12548370
Gateways to Clinical Trials.	2002 Sep	12428432
Accurate mass measurement at enhanced mass-resolution on a triple quadrupole mass-spectrometer for the identification of a reaction impurity and collisionally-induced fragment ions of cabergoline.	2003	12621618
Treatment with cabergoline is associated with weight loss in patients with hyperprolactinemia.	2003 Feb	12582229
Radioimmunoassay of prolactin for the meerkat (Suricata suricatta), a cooperatively breeding carnivore.	2003 Feb 1	12568792
Hyperprolactinemia in men: clinical and biochemical features and response to treatment.	2003 Feb-Mar	12668871
Involvement of PI3'-K, mitogen-activated protein kinase and protein kinase B in the up-regulation of the expression of nNOSalpha and nNOSbeta splicing variants induced by PRL-receptor activation in GH3 cells.	2003 Mar	12614337
Selective control of the estrous cycle of the dog through suppression of estrus and reduction of the length of anestrus.	2003 Mar	12527090
[Macroadenoma of the pituitary gland with moderate hyperprolactinaemia].	2003 Mar 28	12660899

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage for initiation of therapy is 0.25 mg twice a week. Dosage may be increased by 0.25 mg twice weekly up to a dosage of 1 mg twice a week according to the patient’s serum prolactin level. Dosage increases should not occur more rapidly than every 4 weeks.

Route of Administration: Oral

In Vitro Use Guide

Tert-butylhydroperoxide caused a 42+/-4% neuronal death, which was prevented by cabergoline (2 h before) in a concentration-dependent manner (EC(50): 1.24 microM).

Name

Type

Language

CABERGOLINE

Official Name

English

FCE-21336

Code

English

DOSTINEX

Brand Name

English

CABERGOLINE [JAN]

Common Name

English

CABERGOLINE [VANDF]

Common Name

English

VELACTIS

Brand Name

English

CABASER

Brand Name

English

Cabergoline [WHO-DD]

Common Name

English

CABERGOLINE [USP-RS]

Common Name

English

ERGOLINE-8.BETA.-CARBOXAMIDE, N-(3-(DIMETHYLAMINO)PROPYL)-N-((ETHYLAMINO)CARBONYL)-6-(2-PROPENYL)-

Systematic Name

English

CABERGOLINE [ORANGE BOOK]

Common Name

English

FCE 21336

Code

English

CABERGOLINE [USAN]

Common Name

English

1-[(6-Allylergolin-8?-yl)carbonyl]-1-[3-(dimethylamino)propyl]-3-ethylurea

Systematic Name

English

CABERGOLINE [EP MONOGRAPH]

Common Name

English

cabergoline [INN]

Common Name

English

CABERGOLINE [MI]

Common Name

English

CABERGOLINE [MART.]

Common Name

English

CABERGOLINE [USP MONOGRAPH]

Common Name

English

CABERGOLINE [EMA EPAR VETERINARY]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66884