Cabergoline — BrandWiki

Cabergoline

verifiedfields	changed
watchedfields	changed
verifiedrevid	477165198
width	150
image2	Cabergoline.png
width2	225
tradename	Dostinex, others
dailymedid	Cabergoline
routes of administration	Oral
atc prefix	G02
atc suffix	CB03
legal au	S4
legal au comment	‡R1R‡
legal us	Rx-only
bioavailability	50–80% ‡R2R‡
protein bound	Moderately bound (40–42%); concentration-independent
metabolism	Liver, predominately via hydrolysis of the acylurea bond or the urea moiety
elimination half-life	63–69 hours (estimated)
excretion	Urine (22%), feces (60%)
cas number	81409-90-7
pubchem	54746
iuphar ligand	37
drugbank	DB00248
chemspiderid	49452
unii	LL60K9J05T
kegg	D00987
chebi	3286
chembl	1201087
synonyms	N-[3-(Dimethylamino)propyl]-N-(ethylcarbamoyl)-6-(prop-2-en-1-yl)ergoline-8β-carboxamide
iupac name	(6aR,9R,10aR)-N-[3-(dimethylamino)propyl]-N-(ethylcarbamoyl)-7-prop-2-enyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
c	26
h	37
n	5
o	2
smiles	[H][C@]12C[C@@H](C(=O)N(CCCN(C)C)C(=O)NCC)CN(CC=C)[C@]1([H])Cc3c[nH]c4cccc2c34
stdinchi	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
stdinchikey	KORNTPPJEAJQIU-KJXAQDMKSA-N

Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications.[3] It is taken by mouth.

Cabergoline is an ergot derivative and a potent dopamine D2 receptor agonist.[4]

Cabergoline was patented in 1980 and approved for medical use in 1993.[5] It is on the World Health Organization's List of Essential Medicines.[6]

Medical uses

Medical uses of cabergoline include:

Side effects

Side effects are mostly dose dependent. Much more severe side effects are reported for treatment of Parkinson's disease and (off-label treatment) for restless leg syndrome which both typically require very high doses. The side effects are considered mild when used for treatment of hyperprolactinemia and other endocrine disorders or gynecologic indications where the typical dose is one hundredth to one tenth that for Parkinson's disease.

Cabergoline requires slow dose titration (2–4 weeks for hyperprolactinemia, often much longer for other conditions) to minimize side effects. The extremely long bioavailability of the medication may complicate dosing regimens during titration and require particular precautions.

Cabergoline is considered the best tolerable option for hyperprolactinemia treatment although the newer and less tested quinagolide may offer similarly favourable side effect profile with quicker titration times.

Approximately 200 patients with newly diagnosed Parkinson's disease participated in a clinical study of cabergoline monotherapy.[18] Seventy-six (76) percent reported at least one side effect. These side effects were chiefly mild or moderate:

In a combination study with 2,000 patients also treated with levodopa, the incidence and severity of side effects was comparable to monotherapy. Encountered side effects required a termination of cabergoline treatment in 15% of patients. Additional side effects were infrequent cases of hematological side effects, and an occasional increase in liver enzymes or serum creatinine without signs or symptoms.

As with other ergot derivatives, pleuritis, exudative pleura disease, pleura fibrosis, lung fibrosis, and pericarditis are seen. These side effects are noted in less than 2% of patients. They require immediate termination of treatment. Clinical improvement and normalization of X-ray findings are normally seen soon after cabergoline withdrawal. It appears that the dose typically used for treatment of hyperprolactinemia is too low to cause this type of side effects.

GI tract: Side effects were extremely frequent. Fifty-three percent of patients reported side effects. Very frequent: Nausea (30%), constipation (22%), and dry mouth (10%). Frequent: Gastric irritation (7%), vomiting (5%), and dyspepsia (2%).
Psychiatric disturbances and central nervous system (CNS): Altogether 51 percent of patients were affected. Very frequent: Sleep disturbances (somnolence 18%, insomnia 11%), vertigo (27%), and depression (13%). Frequent: dyskinesia (4%) and hallucinations (4%).
Cardiovascular: Approximately 30 percent of patients experienced side effects. Most frequent were hypotension (10%), peripheral edema (14%) and non-specific edema (2%). Arrhythmias were encountered in 4.8%, palpitations in 4.3%, and angina pectoris in 1.4%.

Valvular heart disease

In two studies published in the New England Journal of Medicine on January 4, 2007, cabergoline was implicated along with pergolide in causing valvular heart disease.[19][20] As a result of this, the FDA removed pergolide from the U.S. market on March 29, 2007.[21] Since cabergoline is not approved in the U.S. for Parkinson's Disease, but for hyperprolactinemia, the drug remains on the market. The lower doses required for treatment of hyperprolactinemia have been found to be not associated with clinically significant valvular heart disease or cardiac valve regurgitation.[22][23]

Pharmacology

Pharmacodynamics

Cabergoline is a long-acting dopamine D2 receptor agonist. In-vitro rat studies show a direct inhibitory effect of cabergoline on the prolactin secretion in the lactotroph cells of the pituitary gland and cabergoline decreases serum prolactin levels in reserpinized rats. Although cabergoline is commonly described principally as a D2 receptor agonist, it also possesses significant affinity for the dopamine D3, and D4, serotonin 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C, and α2-adrenergic receptors, as well as moderate/low affinity for the dopamine D1, serotonin 5-HT7, and α1-adrenergic receptors.[24][27][29] Cabergoline functions as a partial or full agonist at all of these receptors except for the 5-HT7, α1-adrenergic, and α2-adrenergic receptors, where it acts as an antagonist.[25][26][27] Cabergoline has been associated with cardiac valvulopathy due to activation of 5-HT2B receptors.[30]

Ergot derivatives like cabergoline have been described as non-hallucinogenic in spite of acting as serotonin 5-HT2A receptor agonists.[31]

Pharmacokinetics

Following a single oral dose, resorption of cabergoline from the gastrointestinal (GI) tract is highly variable, typically occurring within 0.5 to 4 hours. Ingestion with food does not alter its absorption rate. Human bioavailability has not been determined since the drug is intended for oral use only. In mice and rats the absolute bioavailability has been determined to be 30 and 63 percent, respectively. Cabergoline is rapidly and extensively metabolized in the liver and excreted in bile and to a lesser extent in urine. All metabolites are less active than the parental drug or inactive altogether. The human elimination half-life is estimated to be 63 to 68 hours in patients with Parkinson's disease and 79 to 115 hours in patients with pituitary tumors. Average elimination half-life is 80 hours. The metabolism of cabergoline is mediated by unidentified enzymes via a hepatic route and mainly consists of hydrolysis and oxidation by the alkylurea group and oxidation at the alkene.[32][33]

References

Carbelin (Nova Pharmaceuticals Australasia Pty Ltd) Therapeutic Goods Administration (TGA), 13 September 2024, retrieved 15 September 2024^
An evidence-based review of Dopamine receptor agonists in the treatment of Parkinson's disease Neurosciences, 2002^
Cabergoline: MedlinePlus Drug Information medlineplus.gov, retrieved 2023-10-22^
The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies Springer, 1990^
Analogue-based Drug Discovery John Wiley & Sons, 2006^
The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) World Health Organization, 2023^
UK electronic Medicines Compendium Dostinex Tablets Last Updated on eMC Dec 23, 2013^
Comparison of the effect of gonadotropin-releasing hormone agonist and dopamine receptor agonist on uterine myoma growth. Histologic, sonographic, and intra-operative changes Saudi Medical Journal, August 2009^
Medical management of fibroids Best Practice & Research. Clinical Obstetrics & Gynaecology, August 2008^
Effects of acute prolactin manipulation on sexual drive and function in males The Journal of Endocrinology, December 2003^
Cabergoline in the Treatment of Male Orgasmic Disorder-A Retrospective Pilot Analysis Sexual Medicine, March 2016^
Can dopamine agonists reduce the incidence and severity of OHSS in IVF/ICSI treatment cycles? A systematic review and meta-analysis Human Reproduction Update, March 2010^
Cabergoline decreases alcohol drinking and seeking behaviors via glial cell line-derived neurotrophic factor Biological Psychiatry, July 2009^
Effective cabergoline treatment in idiopathic restless legs syndrome Neurology, December 2004^
Preparation and characterization of vaginal suppository of semisynthetic derivatives of ergot alkaloids cabergoline Saudi Pharmaceutical Journal, December 2023^
Cabergoline Use and Pregnancy Outcomes: A Systematic Review Birth Defects Research, March 2025^
Pregnancy outcomes following cabergoline treatment: extended results from a 12-year observational study Clinical Endocrinology, January 2008^
Cabergoline in the treatment of early Parkinson's disease: results of the first year of treatment in a double-blind comparison of cabergoline and levodopa. The PKDS009 Collaborative Study Group Neurology, February 1997^
Dopamine agonists and the risk of cardiac-valve regurgitation The New England Journal of Medicine, January 2007^
Valvular heart disease and the use of dopamine agonists for Parkinson's disease The New England Journal of Medicine, January 2007^
Food and Drug Administration Public Health Advisory Food and Drug Administration, 2007-03-29, retrieved 2007-04-27^
Treatment with low doses of cabergoline is not associated with increased prevalence of cardiac valve regurgitation in patients with hyperprolactinaemia International Journal of Clinical Practice, December 2008^
Low dose cabergoline for hyperprolactinaemia is not associated with clinically significant valvular heart disease European Journal of Endocrinology, October 2008^
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes The Journal of Pharmacology and Experimental Therapeutics, November 2002^
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 The Journal of Pharmacology and Experimental Therapeutics, November 2002^
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes The Journal of Pharmacology and Experimental Therapeutics, November 2002^
Cabergoline: Pharmacology, ocular hypotensive studies in multiple species, and aqueous humor dynamic modulation in the Cynomolgus monkey eyes Experimental Eye Research, March 2009^
PDSP Database – UNC pdsp.unc.edu, retrieved 15 January 2022^
National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Jul 24]. ChapelHill (NC): University of North Carolina. 1998-2013. Available from: PDSP Database – UNC retrieved 2014-03-04^
Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy Journal of Pharmacological and Toxicological Methods, 2014^
Psychedelics: preclinical insights provide directions for future research Neuropsychopharmacology, January 2024^
DOSTINEX cabergoline tablets Pfizer, U.S. Food and Drug Administration, July 2011^
Development and validation of different chromatographic methods for analysis of cabergoline in the presence of its degradation products: studying degradation profile. Chromatographia, October 2019^
Council regulation (EEC) no 1768/92 in the matter of Application No SPC/GB94/012 for a Supplementary Protection Certificate in the name of Farmitalia Carlo Erba S. r. l.^
Espace record: GB 202074566 retrieved 2016-04-17^
US Patent 4526892 – Dimethylaminoalkyl-3-(ergoline-8'.beta.carbonyl)-ureas^
Pharmacodynamic and pharmacokinetic features of cabergoline. Rationale for use in Parkinson's disease Drugs, 1998^
Biochemical and pharmacological studies on cabergoline, a new putative antiparkinsonian drug Soc Neurosci Abs, 1991^
Staff. News: Farmitalia bought by Kabi Pharmacia. Ann Oncol (1993) 4 (5): 345.^
Staff, CNN/Money. April 16, 2003 It's official: Pfizer buys Pharmacia^
FDA approval history^
Drugs@FDA: FDA Approved Drug Products – ANDA 076310 www.accessdata.fda.gov, FDA.gov, retrieved 14 December 2018^
Cabergoline Uses, Side Effects & Warnings^
Effect of cabergoline treatment on Cushing's disease caused by aberrant adrenocorticotropin-secreting macroadenoma Journal of Endocrinological Investigation, December 2004^