Cabergoline

Last updated

Cabergoline
Cabergoline.svg
Clinical data
Trade names Dostinex, others
AHFS/Drugs.com Monograph
License data
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability First-pass effect seen; absolute bioavailability unknown
Protein binding 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%)
Identifiers
  • (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
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.155.380 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C26H37N5O2
Molar mass 451.615 g·mol−1
3D model (JSmol)
  • [H][C@]12C[C@@H](C(=O)N(CCCN(C)C)C(=O)NCC)CN(CC=C)[C@]1([H])Cc3c[nH]c4cccc2c34
  • 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 Yes check.svgY
  • Key:KORNTPPJEAJQIU-KJXAQDMKSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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. [2] It is taken by mouth.

Contents

Cabergoline is an ergot derivative and a potent dopamine D2 receptor agonist. [3]

Cabergoline was patented in 1980 and approved for medical use in 1993. [4] It is on the World Health Organization's List of Essential Medicines. [5]

Medical uses

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 older bromocriptine, though in pregnancy bromocriptine is often still chosen since there is less data on safety in pregnancy for cabergoline.

Off-label

Cabergoline 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 that it has a possible recreational use in reducing or eliminating the male refractory period, thereby allowing men to experience multiple ejaculatory orgasms in rapid succession, and at least two scientific studies support those speculations. [9] [10] : e28–e33  Additionally, a systematic review and meta-analysis concluded that prophylactic treatment with cabergoline reduces the incidence, but not the severity, of ovarian hyperstimulation syndrome (OHSS), without compromising pregnancy outcomes, in females undergoing stimulated cycles of in vitro fertilization (IVF). [11] Also, a study on rats found that cabergoline reduces voluntary alcohol consumption, possibly by increasing GDNF expression in the ventral tegmental area. [12] It may be used in the treatment of restless 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. [13]

Pregnancy and lactation

Relatively little is known about the effects of this medication during pregnancy and lactation. In some cases the related bromocriptine may be an alternative when pregnancy is expected.[ citation needed ]

Contraindications

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.[ 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 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. [15] 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.

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. [16] [17] As a result of this, the FDA removed pergolide from the U.S. market on March 29, 2007. [18] 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. [19] [20]

Interactions

No interactions were noted with levodopa or selegiline. The drug should not be combined with other ergot derivatives. Dopamine antagonists such as antipsychotics and metoclopramide counteract some effects of cabergoline. The use of antihypertensive drugs should be intensively monitored because excessive hypotension may result from the combination.

Pharmacology

Pharmacodynamics

Activities of cabergoline at various sites
SiteAffinity
(Ki [nM])		Efficacy
(Emax [%])		Action
D1 214–32,000 ?Agonist
D2S 0.5–0.62102Super agonist
D2L 0.9575Partial agonist
D3 0.80–1.086Near Full agonist
D4 5649Partial agonist
D5 22 ?Agonist
5-HT1A 1.9–2093Full agonist
5-HT1B 479102Super agonist
5-HT1D 8.768Partial agonist
5-HT2A 4.6–6.294Full agonist
5-HT2B 1.2–9.498Full agonist
5-HT2C 5.8–69296Full agonist
5-HT3 >10,000––
5-HT4 3,000 ? ?
5-HT6 1,300 ? ?
5-HT7 2.5 ?Antagonist
α1A 288–>10,0000Silent antagonist
α1B 60–1,000 ? ?
α1D 166 ? ?
α2A 12–1320Silent antagonist
α2B 17–720Silent antagonist
α2C 22–3640Silent 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). [21] Negligible affinity (>10,000 nM) for various other receptors (β1- and β2-adrenergic, adenosine, GABA, glutamate, glycine, nicotinic acetylcholine, opioid, prostanoid). [22] Sources: [21] [23] [24] [22] [25]

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.[ citation needed ] 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. [21] [22] [26] Cabergoline functions as an 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. [23] [24] [22] Cabergoline has been associated with cardiac valvulopathy due to activation of 5-HT2B receptors. [27]

Ergot derivatives like cabergoline have been described as non-hallucinogenic in spite of acting as serotonin 5-HT2A receptor agonists. [28]

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. [29] [30]

CabergolineMetabolism.png

History

Cabergoline was first synthesized by scientists working for the Italian drug company Farmitalia-Carlo Erba in Milan who were experimenting with semisynthetic derivatives of the ergot alkaloids, and a patent application was filed in 1980. [31] [32] [33] The first publication was a scientific abstract at the Society for Neuroscience meeting in 1991. [34] [35]

Farmitalia-Carlo Erba was acquired by Pharmacia in 1993, [36] which in turn was acquired by Pfizer in 2003. [37]

Cabergoline was first marketed in The Netherlands as Dostinex in 1992. [31] The drug was approved by the FDA on December 23, 1996. [38] It went generic in late 2005 following US patent expiration. [39]

Society and culture

Brand names

Brand names of cabergoline include Cabaser, Dostinex, Galastop (veterinary), and Kelactin (veterinary), among others. [40]

Research

Cabergoline was studied in one person with Cushing's disease, to lower adrenocorticotropic hormone (ACTH) levels and cause regression of ACTH-producing pituitary adenomas. [41]

Related Research Articles

<span class="mw-page-title-main">Hyperprolactinaemia</span> Excess of prolactin hormone in the blood

Hyperprolactinaemia is a condition characterized by abnormally high levels of prolactin in the blood. In women, normal prolactin levels average to about 13 ng/mL, while in men, they average 5 ng/mL. The upper normal limit of serum prolactin is typically between 15 to 25 ng/mL for both genders. Levels exceeding this range indicate hyperprolactinemia.

<span class="mw-page-title-main">Ergoline</span> Chemical compound

Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of these are implicated in the condition ergotism, which can take a convulsive form or a gangrenous form. Even so, many ergoline alkaloids have been found to be clinically useful. Annual world production of ergot alkaloids has been estimated at 5,000–8,000 kg of all ergopeptines and 10,000–15,000 kg of lysergic acid, used primarily in the manufacture of semi-synthetic derivatives.

<span class="mw-page-title-main">Bromocriptine</span> Dopamine agonist medication

Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes.

<span class="mw-page-title-main">Pergolide</span> Dopamine agonist medication

Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced dopamine synthesis in the substantia nigra of the brain. Pergolide acts on many of the same receptors as dopamine to increase receptor activity.

<span class="mw-page-title-main">Ergoloid</span> Chemical compound

Ergoloid mesylates (USAN), co-dergocrine mesilate (BAN) or dihydroergotoxine mesylate, trade name Hydergine, is a mixture of the methanesulfonate salts of three dihydrogenated ergot alkaloids.

<span class="mw-page-title-main">Amoxapine</span> Tricyclic antidepressant medication

Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCA). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1980, approximately 10 to 20 years after most of the other TCAs were introduced in the United States.

<span class="mw-page-title-main">Domperidone</span> Peripheral D2 receptor antagonist

Domperidone, sold under the brand name Motilium among others, is a dopamine antagonist medication which is used to treat nausea and vomiting and certain gastrointestinal problems like gastroparesis. It raises the level of prolactin in the human body and is used off label to induce and promote breast milk production. It may be taken by mouth or rectally.

<span class="mw-page-title-main">Prolactinoma</span> Pituitary gland tumor which secretes the hormone prolactin

A prolactinoma is a tumor (adenoma) of the pituitary gland that produces the hormone prolactin. It is the most common type of functioning pituitary tumor. Symptoms of prolactinoma are due to abnormally high levels of prolactin in the blood (hyperprolactinemia), or due to pressure of the tumor on surrounding brain tissue and/or the optic nerves. Based on its size, a prolactinoma may be classified as a microprolactinoma or a macroprolactinoma.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.

<span class="mw-page-title-main">Ropinirole</span> Dopamine agonist medication

Ropinirole, sold under the brand name Requip among others, is a medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). It is taken by mouth.

<span class="mw-page-title-main">Dopamine agonist</span> Compound that activates dopamine receptors

A dopamine agonist is a compound that activates dopamine receptors. There are two families of dopamine receptors, D1-like and D2-like. They are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are primarily used in the treatment of the motor symptoms of Parkinson's disease, and to a lesser extent, in hyperprolactinemia and restless legs syndrome. They are also used off-label in the treatment of clinical depression. Impulse control disorders are associated with the use of dopamine agonists for whatever condition.

<span class="mw-page-title-main">Lisuride</span> Chemical compound

Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.

<span class="mw-page-title-main">Rotigotine</span> Dopamine agonist medication

Rotigotine, sold under the brand name Neupro among others, is a dopamine agonist of the non-ergoline class of medications indicated for the treatment of Parkinson's disease and restless legs syndrome. It is formulated as a once-daily transdermal patch which provides a slow and constant supply of the drug over the course of 24 hours.

In the management of Parkinson's disease, due to the chronic nature of Parkinson's disease (PD), a broad-based program is needed that includes patient and family education, support-group services, general wellness maintenance, exercise, and nutrition. At present, no cure for the disease is known, but medications or surgery can provide relief from the symptoms.

<span class="mw-page-title-main">Dihydroergocryptine</span> Chemical compound

Dihydroergocryptine (DHEC), sold under the brand names Almirid and Cripar among others, is a dopamine agonist of the ergoline group that is used as an antiparkinson agent in the treatment of Parkinson's disease. It is taken by mouth.

Cardiac fibrosis commonly refers to the excess deposition of extracellular matrix in the cardiac muscle, but the term may also refer to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts. Fibrotic cardiac muscle is stiffer and less compliant and is seen in the progression to heart failure. The description below focuses on a specific mechanism of valvular pathology but there are other causes of valve pathology and fibrosis of the cardiac muscle.

<span class="mw-page-title-main">Metergoline</span> Chemical compound

Metergoline, also known as methergoline and sold under the brand names Contralac (veterinary) and Liserdol (clinical), is a monoaminergic medication of the ergoline group which is used as a prolactin inhibitor in the treatment of hyperprolactinemia and to suppress lactation.

<span class="mw-page-title-main">Pimavanserin</span> Atypical antipsychotic medication

Pimavanserin, sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis. It is taken by mouth.

<span class="mw-page-title-main">Prolactin modulator</span> Drug class

A prolactin modulator is a drug which affects the hypothalamic–pituitary–prolactin axis by modulating the secretion of the pituitary hormone prolactin from the anterior pituitary gland. Prolactin inhibitors suppress and prolactin releasers induce the secretion of prolactin, respectively.

Female fertility agents are medications that improve female’s ability to conceive pregnancy. These agents are prescribed for infertile female who fails to conceive pregnancy after 1-year of regular and unprotected sexual intercourse. The following will cover the advancements of female fertility agents, major causes of female infertility. Next, it emphasizes on common female fertility agents in terms of their mechanism of action, side effects, fetal consideration and clinical application and ended up by the introduction of supplements and herbal medicines for female infertility.

References

  1. ↑ "Carbelin (Nova Pharmaceuticals Australasia Pty Ltd)". Therapeutic Goods Administration (TGA). 13 September 2024. Retrieved 15 September 2024.
  2. ↑ "Cabergoline: MedlinePlus Drug Information". medlineplus.gov. Retrieved 2023-10-22.
  3. ↑ Elks J, Ganellin CR (1990). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 204–.
  4. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 533. ISBN   9783527607495.
  5. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  6. ↑ UK electronic Medicines Compendium Dostinex Tablets Last Updated on eMC Dec 23, 2013
  7. ↑ Sayyah-Melli M, Tehrani-Gadim S, Dastranj-Tabrizi A, Gatrehsamani F, Morteza G, Ouladesahebmadarek E, et al. (August 2009). "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. 30 (8): 1024–1033. PMID   19668882.
  8. ↑ Sankaran S, Manyonda IT (August 2008). "Medical management of fibroids" (PDF). Best Practice & Research. Clinical Obstetrics & Gynaecology. 22 (4): 655–676. doi:10.1016/j.bpobgyn.2008.03.001. PMID   18468953.
  9. ↑ Krüger TH, Haake P, Haverkamp J, Krämer M, Exton MS, Saller B, et al. (December 2003). "Effects of acute prolactin manipulation on sexual drive and function in males". The Journal of Endocrinology. 179 (3): 357–365. CiteSeerX   10.1.1.484.4005 . doi:10.1677/joe.0.1790357. PMID   14656205.
  10. ↑ Hollander AB, Pastuszak AW, Hsieh TC, Johnson WG, Scovell JM, Mai CK, et al. (March 2016). "Cabergoline in the Treatment of Male Orgasmic Disorder-A Retrospective Pilot Analysis". Sexual Medicine. 4 (1): e28–e33. doi:10.1016/j.esxm.2015.09.001. PMC   4822480 . PMID   26944776.
  11. ↑ Youssef MA, van Wely M, Hassan MA, Al-Inany HG, Mochtar M, Khattab S, et al. (March 2010). "Can dopamine agonists reduce the incidence and severity of OHSS in IVF/ICSI treatment cycles? A systematic review and meta-analysis". Human Reproduction Update. 16 (5): 459–466. doi: 10.1093/humupd/dmq006 . PMID   20354100.
  12. ↑ Carnicella S, Ahmadiantehrani S, He DY, Nielsen CK, Bartlett SE, Janak PH, et al. (July 2009). "Cabergoline decreases alcohol drinking and seeking behaviors via glial cell line-derived neurotrophic factor". Biological Psychiatry. 66 (2): 146–153. doi:10.1016/j.biopsych.2008.12.022. PMC   2895406 . PMID   19232578.
  13. ↑ Rahmanian-Devin P, Fadaei MR, Mashreghi M, Askari VR (December 2023). "Preparation and characterization of vaginal suppository of semisynthetic derivatives of ergot alkaloids cabergoline". Saudi Pharmaceutical Journal. 31 (12): 101849. doi:10.1016/j.jsps.2023.101849. PMC   10663909 . PMID   38028218.
  14. ↑ Colao A, Abs R, Bárcena DG, Chanson P, Paulus W, Kleinberg DL (January 2008). "Pregnancy outcomes following cabergoline treatment: extended results from a 12-year observational study". Clinical Endocrinology. 68 (1): 66–71. doi:10.1111/j.1365-2265.2007.03000.x. PMID   17760883. S2CID   38408935.
  15. ↑ Rinne UK, Bracco F, Chouza C, Dupont E, Gershanik O, Marti Masso JF, et al. (February 1997). "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. 48 (2): 363–368. doi:10.1212/WNL.48.2.363. PMID   9040722. S2CID   34955541.
  16. ↑ Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E (January 2007). "Dopamine agonists and the risk of cardiac-valve regurgitation". The New England Journal of Medicine. 356 (1): 29–38. doi: 10.1056/NEJMoa062222 . PMID   17202453.
  17. ↑ Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G (January 2007). "Valvular heart disease and the use of dopamine agonists for Parkinson's disease". The New England Journal of Medicine. 356 (1): 39–46. doi: 10.1056/NEJMoa054830 . PMID   17202454.
  18. ↑ "Food and Drug Administration Public Health Advisory". Food and Drug Administration . 2007-03-29. Archived from the original on 2007-04-08. Retrieved 2007-04-27.
  19. ↑ Bogazzi F, Buralli S, Manetti L, Raffaelli V, Cigni T, Lombardi M, et al. (December 2008). "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. 62 (12): 1864–1869. doi: 10.1111/j.1742-1241.2008.01779.x . PMID   18462372. S2CID   7822137.
  20. ↑ Wakil A, Rigby AS, Clark AL, Kallvikbacka-Bennett A, Atkin SL (October 2008). "Low dose cabergoline for hyperprolactinaemia is not associated with clinically significant valvular heart disease". European Journal of Endocrinology. 159 (4): R11–R14. doi: 10.1530/EJE-08-0365 . PMID   18625690.
  21. 1 2 3 Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A (November 2002). "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. 303 (2): 791–804. doi:10.1124/jpet.102.039867. PMID   12388666. S2CID   6200455.
  22. 1 2 3 4 Sharif NA, McLaughlin MA, Kelly CR, Katoli P, Drace C, Husain S, et al. (March 2009). "Cabergoline: Pharmacology, ocular hypotensive studies in multiple species, and aqueous humor dynamic modulation in the Cynomolgus monkey eyes". Experimental Eye Research. 88 (3): 386–397. doi:10.1016/j.exer.2008.10.003. PMID   18992242.
  23. 1 2 Newman-Tancredi A, Cussac D, Audinot V, Nicolas JP, De Ceuninck F, Boutin JA, et al. (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. 303 (2): 805–814. doi:10.1124/jpet.102.039875. PMID   12388667. S2CID   35238120.
  24. 1 2 Newman-Tancredi A, Cussac D, Quentric Y, Touzard M, Verrièle L, Carpentier N, et al. (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. 303 (2): 815–822. doi:10.1124/jpet.102.039883. PMID   12388668. S2CID   19260572.
  25. ↑ "PDSP Database - UNC". pdsp.unc.edu. Archived from the original on 13 April 2021. Retrieved 15 January 2022.
  26. ↑ 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". Archived from the original on 2013-11-08. Retrieved 2014-03-04.
  27. ↑ Cavero I, Guillon JM (2014). "Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy". Journal of Pharmacological and Toxicological Methods. 69 (2): 150–161. doi:10.1016/j.vascn.2013.12.004. PMID   24361689.
  28. ↑ Gumpper RH, Roth BL (January 2024). "Psychedelics: preclinical insights provide directions for future research". Neuropsychopharmacology. 49 (1): 119–127. doi:10.1038/s41386-023-01567-7. PMC  10700551. PMID   36932180.
  29. ↑ "DOSTINEX cabergoline tablets" (PDF). Pfizer. U.S. Food and Drug Administration. July 2011.
  30. ↑ Farid NF, Abdelwahab NS (October 2019). "Development and validation of different chromatographic methods for analysis of cabergoline in the presence of its degradation products: studying degradation profile". Chromatographia. 82 (10): 1555–1569. doi:10.1007/s10337-019-03763-4.
  31. 1 2 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.
  32. ↑ Espace record: GB 202074566
  33. ↑ US Patent 4526892 - Dimethylaminoalkyl-3-(ergoline-8'.beta.carbonyl)-ureas
  34. ↑ Fariello RG (1998). "Pharmacodynamic and pharmacokinetic features of cabergoline. Rationale for use in Parkinson's disease". Drugs. 55 (Suppl 1): 10–16. doi:10.2165/00003495-199855001-00002. PMID   9483165. S2CID   46973281.
  35. ↑ Carfagna N, Caccia C, Buonamici M, Cervini MA, Cavanus S, Fornaretto MG, et al. (1991). "Biochemical and pharmacological studies on cabergoline, a new putative antiparkinsonian drug". Soc Neurosci Abs. 17: 1075.
  36. ↑ Staff. News: Farmitalia bought by Kabi Pharmacia [ permanent dead link ]. Ann Oncol (1993) 4 (5): 345.
  37. ↑ Staff, CNN/Money. April 16, 2003 It's official: Pfizer buys Pharmacia
  38. ↑ FDA approval history
  39. ↑ "Drugs@FDA: FDA Approved Drug Products - ANDA 076310". www.accessdata.fda.gov. FDA.gov. Retrieved 14 December 2018.
  40. ↑ "Cabergoline Uses, Side Effects & Warnings". Archived from the original on 2015-12-30.
  41. ↑ Miyoshi T, Otsuka F, Takeda M, Inagaki K, Suzuki J, Ogura T, et al. (December 2004). "Effect of cabergoline treatment on Cushing's disease caused by aberrant adrenocorticotropin-secreting macroadenoma". Journal of Endocrinological Investigation. 27 (11): 1055–1059. doi:10.1007/bf03345309. PMID   15754738. S2CID   6660262.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.