Cabergoline
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| Non-proprietary name | Cabergoline | ||||||||||||||||||
| other names |
(8 β ) - N - [3- (Dimethylamino) propyl] - N - [(ethylamino) carbonyl] -6- (2-propenyl) -ergoline-8-carboxamide ( IUPAC ) |
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| Molecular formula | C 26 H 37 N 5 O 2 | ||||||||||||||||||
| Brief description |
white to almost white, crystalline, polymorphic powder |
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| Drug information | |||||||||||||||||||
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| Drug class |
Parkinson’s drugs , prolactin inhibitors |
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| Molar mass | 451.61 g · mol -1 | ||||||||||||||||||
| Physical state |
firmly |
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| Melting point |
102-104 ° C |
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| solubility |
practically insoluble in water, slightly soluble in ethanol , very sparingly soluble in n -hexane |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||||||||
Cabergoline is a drug derived from ergot alkaloids . It acts as a primary dopamine D 2 agonist . Cabergoline is used in human medicine as a remedy for Parkinson's disease , for weaning and for galactorrhea or prolactin excess. In veterinary medicine, the active ingredient is at pseudopregnancy , for Abort introduction, for estrus induction in mammary tumors and Pyometratherapie used.
Pharmacological properties
As an agonist at dopamine receptors, which belong to the G-protein-coupled receptors , cabergoline mimics the action of the neurotransmitter dopamine . It has a high specific affinity for the D 2 receptors of the cells that produce prolactin in the anterior pituitary gland , which leads to an inhibition of the secretion of this hormone .
The lipid solubility is 2.855, the plasma half-life is 63–69 hours in humans and 17–24 hours in dogs. It is absorbed orally and 40–42 percent of the active ingredient is bound to plasma proteins in the body. Cabergoline is mainly metabolized by cleavage in the liver ; the enzyme responsible for this has not yet been identified. The metabolism of cabergoline is only slightly dependent on the cytochrome P450 . 97% of it is excreted in the faeces, so no adjustment is necessary in the event of renal insufficiency . The drug is contraindicated during pregnancy.
Clinical information
Application areas (indications)
Human medicine
In human medicine, the drug is used for two main indications and is therefore classified under two different ATC codes : One area of application is neurological diseases of the extrapyramidal motor system such as Parkinson's disease (ATC code N04BC06) and restless legs syndrome . The second area of application are gynecological diseases (ATC code G02CB03) with increased prolactin secretion, such as B. prolactinomas or weaning , although in Germany there is a license only for primary weaning. Furthermore, in specific cases, the agent is used in significantly lower doses to treat acromegaly , if the hormone-producing tissue could not be completely removed after an operation on the pituitary gland .
Veterinary medicine
In veterinary medicine, cabergoline is approved for dogs and dairy cows.
The most important area of application in dogs is false pregnancy ( lactatio falsa ), an atavism in dogs that can occur 6 to 12 weeks after heat and is associated with increased prolactin secretion. Here the active ingredient is administered once a day for 8 days. Chronic pseudopregnancy, which occurs when the ovaries are removed during pseudopregnancy , can also be treated in most cases with cabergoline, although the prolactin level is usually not increased. Cabergoline can also be used to successfully treat pseudo-pregnancy in house cats and house rabbits .
In addition, cabergoline can also be used to prevent milk production in dogs and cats during normal lactation , e.g. B. can be used after stillbirths or the death of the puppies.
Since prolactin is the most important luteal- preserving hormone in dogs in later pregnancy , cabergoline can be used together with prostaglandin F2α to induce abortion from day 23 of gestation . Cabergoline alone is unsafe before the 40th day of pregnancy; after the 48th day, premature birth is triggered. An abortion can also be triggered in cats between the 34th and 42nd day of gestation.
Another area of application are tumors of the mammary gland . The risk of developing such tumors increases with the number of pseudopregnations. Cabergoline can be used here before the operation to reduce the swelling of the breasts and thus make the operation easier; benign tumors can even regress completely.
Cabergoline can also be used to induce heat in dogs. After an oestrus cycle, dogs go into a period of rest ( anestrus ) for several months , which can be shortened with the administration of cabergoline. The exact hormonal mechanism of action for this is not known.
Since prolactin maintains the corpus luteum function and thus the production of progesterone, cabergoline can also be used in dogs for the conservative treatment of uterine suppuration ( pyometra ). It leads to an opening of the cervix , after which prostaglandin can be applied to empty the pus. A cure was also achieved in 7 out of 10 cases of glandular-cystic hyperplasia of the endometrium .
Cabergoline is used to dry off dairy cows .
Use during pregnancy and breastfeeding
Pregnancy : Animal experiments have not shown any teratogenic effects, but there is insufficient experience in humans with its use during pregnancy, so that cabergoline should not be used during pregnancy for safety reasons. Pregnancy should be ruled out before treatment begins and contraception should be avoided during treatment . Lactation : Due to the active principle of cabergoline, impairment of lactation (milk flow) is to be expected. No data are available on the transmission of cabergoline through breast milk, so breastfeeding is not recommended during treatment.
Adverse effects (side effects)
The occurrence of side effects is dose-dependent with cabergoline; in short-term treatments such as weaning, these rarely occur. Cabergoline is regarded as the dopaminergic with the fewest side effects and very good patient compliance .
When using cabergoline, side effects such as tiredness / drowsiness, dizziness, nausea, stomach pain and movement disorders ( dyskinesia ) and a drop in blood pressure have been observed. In the case of poisoning in particular, confusion and hallucinations can also occur.
Because of the severe fibrotic cardiac valvulopathy (heart valve damage), which occurred repeatedly with ergot alkaloids, to which the substance belongs, and which were shown in repeated case-control studies (not most recently on January 4, 2007 in the New England Journal of Medicine ), a For long-term use, an appropriate cardiac evaluation is recommended in all patients.
In addition, side effects such as gambling addiction, increased sex drive and binge eating are reported for all dopamine agonists, which the Federal Institute for Drugs and Medical Devices (BfArM) issued on July 30, 2007, prompting the manufacturers of all dopamine agonists to request to explicitly name the dangers of "gambling addiction, increased libido and hypersexuality" in the package inserts. It declared the term "obsessive-compulsive disorder" to be insufficient. According to an American study on Parkinson's patients, the complications can be assumed to be not just isolated cases. At the University of Pennsylvania, neurologist Daniel Weintraub determined that more than 17% of those affected were more than 17% of 3090 test subjects who received pramipexole (a non-ergot dopamine agonist).
Numerous side effects were noted in dairy cows shortly after the product Velactis was launched , mainly bedding, low temperature, hypocalcemia, rumen motor disorders , diarrhea, circulatory disorders and ataxias . There were also deaths. The approval will therefore be checked again in July 2016.
literature
- J. Korrell: The prolactin inhibitor cabergoline. In: Small animal specifically. Vol. 9, No. 2, 2006, pp. 4-7.
Trade names
Cabaser (CH), Cabaseril (D, A), Dostinex (D, A, CH) and various generics (D, A)
In veterinary medicine , cabergoline is commercially available under the trade names Galastop , GalactoFin , Laktostop and Velactis .
Web links
- Entry on osaterone acetate at Vetpharm, accessed on August 11, 2012.
Individual evidence
- ↑ a b c CABERGOLINE CRS data sheet (PDF) at EDQM , accessed on March 6, 2009.
- ↑ Entry on cabergoline. In: Römpp Online . Georg Thieme Verlag, accessed on June 1, 2014.
- ↑ a b Data sheet Cabergoline, ≥98% (HPLC) from Sigma-Aldrich , accessed on October 31, 2016 ( PDF ).
- ↑ Beverly MK Biller: Cabergoline - A New Dopamine Agonist for the Therapy of Prolactinoma.
- ↑ FDA: Dostinex (cabergoline) Tablets , August 2011.
- ↑ Pharmaceutical newspaper: substance abuse disorders by dopamine agonists , issue 35/2010.
- ↑ Dt. TAB. 64 (2016), No. 7, p. 978.
