 | This articleneeds morereliable medical references forverification or relies too heavily onprimary sources. Please review the contents of the article andadd the appropriate references if you can. Unsourced or poorly sourced material may be challenged andremoved.Find sources: "Cabergoline" – news ·newspapers ·books ·scholar ·JSTOR(August 2023) |
 | |
 | |
| Clinical data | |
|---|---|
| Trade names | Dostinex, others |
| Other names | N-[3-(Dimethylamino)propyl]-N-(ethylcarbamoyl)-6-(prop-2-en-1-yl)ergoline-8β-carboxamide |
| AHFS/Drugs.com | Monograph |
| License data | |
| Routes of administration | Oral |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 50 - 80%[2] |
| Protein binding | Moderately bound (40–42%); concentration-independent |
| Metabolism | Liver, predominately via hydrolysis of theacylurea bond or the urea moiety |
| Eliminationhalf-life | 63–69 hours (estimated) |
| Excretion | Urine (22%), feces (60%) |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| IUPHAR/BPS | |
| DrugBank |
|
| ChemSpider |
|
| UNII | |
| KEGG |
|
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.155.380 |
| Chemical and physical data | |
| Formula | C26H37N5O2 |
| Molar mass | 451.615 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
 N Y (what is this?) (verify) | |
Cabergoline, sold under the brand nameDostinex among others, is adopaminergic medication used in the treatment ofhigh prolactin levels,prolactinomas,Parkinson's disease, and for other indications.[3] It is takenby mouth.
Cabergoline is anergot derivative and a potentdopamineD2 receptoragonist.[4]
Cabergoline waspatented in 1980 and approved for medical use in 1993.[5] It is on theWorld Health Organization's List of Essential Medicines.[6]
Medical uses of cabergoline include:
Cabergoline is frequently used as a first-line agent in the management of prolactinomas due to its higher affinity for D2 receptor sites, less severe side effects, and more convenient dosing schedule than the olderbromocriptine, though in pregnancy bromocriptine is often still chosen since there is less data on safety in pregnancy for cabergoline.
Cabergoline has at times been used as an adjunct toSSRIantidepressants as there is some evidence that it counteracts certainside effects of thosedrugs, such as reducedlibido andanorgasmia. It also has been suggested that it has a possiblerecreational use in reducing or eliminating the malerefractory period, thereby allowing men to experience multiple ejaculatory orgasms in rapid succession, and at least two scientific studies support those speculations.[10][11]: e28–e33 Additionally, a systematic review and meta-analysis concluded that prophylactic treatment with cabergoline reduces the incidence, but not the severity, ofovarian hyperstimulation syndrome (OHSS), without compromising pregnancy outcomes, in females undergoing stimulated cycles ofin vitro fertilization (IVF).[12] Also, a study on rats found that cabergoline reduces voluntary alcohol consumption, possibly by increasingGDNF expression in theventral tegmental area.[13] It may be used in the treatment ofrestless legs syndrome.[citation needed]. Oral administration of cabergoline was faced with gastrointestinal problems which cause poor compliance in patients. One of the preferred solutions is to use non-oral dosage forms like suppositories. Vaginal suppositories have ease of use and could hinder gastrointestinal effects of cabergoline.[14]
Relatively little is known about the effects of this medication during pregnancy and lactation. In some cases the relatedbromocriptine may be an alternative when pregnancy is expected.[citation needed]
Contraindications of cabergoline include:
Side effects are mostly dose dependent. Much more severe side effects are reported for treatment of Parkinson's disease and (off-label treatment) forrestless 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.[citation needed]
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 testedquinagolide may offer similarly favourable side effect profile with quicker titration times.
Approximately 200 patients with newly diagnosed Parkinson's disease participated in aclinical study of cabergoline monotherapy.[16] 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 ofhematological side effects, and an occasional increase in liverenzymes orserumcreatinine withoutsigns orsymptoms.
As with other ergot derivatives,pleuritis,exudative pleura disease, pleurafibrosis,lung fibrosis, andpericarditis are seen. These side effects are noted in less than 2% of patients. They require immediate termination of treatment. Clinical improvement and normalization ofX-ray findings are normally seen soon after cabergolinewithdrawal. It appears that the dose typically used for treatment of hyperprolactinemia is too low to cause this type of side effects.
In two studies published in theNew England Journal of Medicine on January 4, 2007, cabergoline was implicated along withpergolide in causingvalvular heart disease.[17][18] As a result of this, theFDA removed pergolide from the U.S. market on March 29, 2007.[19] 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 benot associated with clinically significant valvular heart disease or cardiac valve regurgitation.[20][21]
 | This sectiondoes notcite anysources. Please helpimprove this section byadding citations to reliable sources. Unsourced material may be challenged andremoved.(August 2023) (Learn how and when to remove this message) |
Nointeractions were noted with levodopa orselegiline. The drug should not be combined with other ergot derivatives. Dopamineantagonists such asantipsychotics andmetoclopramide counteract some effects of cabergoline. The use ofantihypertensive drugs should be intensively monitored because excessive hypotension may result from the combination.
| Site | Affinity (Ki [nM]) | Efficacy (Emax [%]) | Action |
|---|---|---|---|
| D1 | 214–32,000 | ? | Agonist |
| D2S | 0.5–0.62 | 102 | Superagonist |
| D2L | 0.95 | 75 | Partial agonist |
| D3 | 0.80–1.0 | 86 | Full agonist |
| D4 | 56 | 49 | Partial agonist |
| D5 | 22 | ? | Agonist |
| 5-HT1A | 1.9–20 | 93 | Full agonist |
| 5-HT1B | 479 | 102 | Superagonist |
| 5-HT1D | 8.7 | 68 | Partial agonist |
| 5-HT2A | 4.6–6.2 | 94 | Full agonist |
| 5-HT2B | 1.2–9.4 | 98 | Full agonist |
| 5-HT2C | 5.8–692 | 96 | Full agonist |
| 5-HT3 | >10,000 | – | – |
| 5-HT4 | 3,000 | ? | ? |
| 5-HT6 | 1,300 | ? | ? |
| 5-HT7 | 2.5 | ? | Antagonist |
| α1A | 288–>10,000 | 0 | Binder |
| α1B | 60–1,000 | ? | Binder |
| α1D | 166 | ? | Binder |
| α2A | 12–132 | 0 | Antagonist |
| α2B | 17–72 | 0 | Antagonist |
| α2C | 22–364 | 0 | Antagonist |
| α2D | 3.6 | ? | ? |
| H1 | 1,380 | ? | ? |
| M1 | >10,000 | – | – |
| SERT | >10,000 | – | – |
| Notes: All sites are human except α2D-adrenergic, which is rat (no human counterpart).[22] Negligible affinity (>10,000 nM) for various other receptors (β1- andβ2-adrenergic,adenosine,GABA,glutamate,glycine,nicotinic acetylcholine,opioid,prostanoid).[23]Sources:[22][24][25][23][26] | |||
Cabergoline is a long-actingdopamineD2 receptoragonist.In-vitro rat studies show a direct inhibitory effect of cabergoline on theprolactin secretion in thelactotroph cells of thepituitary gland and cabergoline decreases serum prolactin levels inreserpinized rats.[citation needed] Although cabergoline is commonly described principally as a D2 receptor agonist, it also possesses significantaffinity for the dopamineD3, andD4,serotonin5-HT1A,5-HT2A,5-HT2B, and5-HT2C, andα2-adrenergicreceptors, as well as moderate/low affinity for the dopamineD1, serotonin5-HT7, andα1-adrenergic receptors.[22][23][27] Cabergoline functions as apartial orfull agonist at all of these receptors except for the 5-HT7, α1-adrenergic, and α2-adrenergic receptors, where it acts as anantagonist.[24][25][23] Cabergoline has been associated withcardiac valvulopathy due to activation of 5-HT2B receptors.[28]
Ergot derivatives like cabergoline have been described as non-hallucinogenic in spite of acting as serotonin 5-HT2A receptor agonists.[29]
| This sectiondoes notcite anysources. Please helpimprove this section byadding citations to reliable sources. Unsourced material may be challenged andremoved.(August 2023) (Learn how and when to remove this message) |
Following a single oraldose, resorption of cabergoline from thegastrointestinal (GI) tract is highly variable, typically occurring within 0.5 to 4 hours. Ingestion withfood does not alter its absorption rate.Humanbioavailability has not been determined since the drug is intended for oral use only. Inmice andrats the absolute bioavailability has been determined to be 30 and 63 percent, respectively. Cabergoline is rapidly and extensivelymetabolized in theliver and excreted inbile and to a lesser extent inurine. Allmetabolites are less active than the parental drug or inactive altogether. The human eliminationhalf-life is estimated to be 63 to 68 hours in patients withParkinson's disease and 79 to 115 hours in patients withpituitarytumors. Average eliminationhalf-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.[30][31]
Cabergoline was first synthesized by scientists working for the Italian drug companyFarmitalia-Carlo Erba inMilan who were experimenting with semisynthetic derivatives of theergot alkaloids, and a patent application was filed in 1980.[32][33][34] The first publication was a scientific abstract at the Society for Neuroscience meeting in 1991.[35][36]
Farmitalia-Carlo Erba was acquired byPharmacia in 1993,[37] which in turn was acquired byPfizer in 2003.[38]
Cabergoline was first marketed in The Netherlands as Dostinex in 1992.[32] The drug was approved by the FDA on December 23, 1996.[39] It wentgeneric in late 2005 following US patent expiration.[40]
Brand names of cabergoline include Cabaser, Dostinex, Galastop (veterinary), and Kelactin (veterinary), among others.[41]
Cabergoline was studied in one person withCushing's disease, to loweradrenocorticotropic hormone (ACTH) levels and cause regression of ACTH-producing pituitary adenomas.[42]