81409-90-7 Usage
Uses
Used in Neurology:
Cabergoline is used as a dopamine D2-receptor agonist for the treatment of Parkinson's disease. It helps manage the symptoms of the disease by increasing dopamine levels in the brain.
Used in Endocrinology:
Cabergoline is used as a prolactin inhibitor for the management of hyperprolactinemic disorders, either idiopathic or caused by pituitary adenomas. It effectively reduces prolactin levels, alleviating symptoms associated with hyperprolactinemia.
Used in Obstetrics:
Cabergoline is used as a receptor stimulant for inhibiting puerperal lactation. A single 1 mg dose can effectively prevent lactation for up to 14 days, offering a superior alternative to daily regimen drugs.
Used in Oncology:
Cabergoline is in clinical trials for breast cancer treatment. Its potential application in this field is still under investigation.
Cabergoline is also being studied for its potential use in treating other conditions, such as macroprolactinomas and acromegaly. However, it is essential to note that the uses mentioned above are based on the provided materials, and the actual applications may vary depending on clinical trials, research, and regulatory approvals.
Originator
Kabi Pharmacia (Sweden)
Manufacturing Process
A mixture of 6-(2-propenyl)-8β-carboxy-ergoline and N-(3-
dimethylaminopropyl)-N-ethyl carbodiimide in tetrahydrofuran were refluxed,
with stirring and under nitrogen, for 24 h. The resultant solution was
evaporated in vacuo to dryness and the residue taken up with chloroform and 5% sodium hydroxide solution. The organic phase was separated, dried over
anhydrous sodium sulfate and evaporated in vacuo. The residue was
chromatographed on silica (eluant chloroform with 1% methanol) to give the
title compound N-(3-(dimethylamino)propyl)-N-((ethylamino)carbonyl)-8β-
carboxamide-6-(2-propenyl)ergoline.
Biological Activity
Selective D 2 -like dopamine receptor agonist (K i values are 0.7, 1.5, 9.0 and 165 nM for D 2 , D 3 , D 4 and D 5 receptors respectively) that also displays high affinity for several serotonin receptor subtypes (K i = 1.2-20.0 nM for 5-HT 1A , 5-HT 1D , 5-HT 2A and 5-HT 2B ). Inhibits secretion of prolactin and growth hormone and reverses levodopa-induced dyskinesias in Parkinsonian monkeys.
Biochem/physiol Actions
Cabergoline, a lysergic acid amide derivative, is a potent dopamine D2 receptor agonist. It also acts on dopamine receptors in lactophilic hypothalamus cells to suppress prolactin production in the pituitary gland. It has been used for monotherapy of Parkinson′s disease in the early phase; combination therapy, together with levodopa and a decarboxylase inhibitor such as carbidopa, in progressive-phase Parkinson′s disease and adjunctive therapy of prolactin-producing pituitary gland tumors (microprolactinomas).
Clinical Use
Endocrine disorders
Adjunct to levodopa (with a decarboxylase inhibitor)
in Parkinson’s disease
Inhibition / suppression of lactation
Veterinary Drugs and Treatments
For dogs, cabergoline may be useful for inducing estrus, treatment
of primary or secondary anestrus, pseudopregnancy, and pregnancy
termination in the second half of pregnancy. Cabergoline may be
useful in treating some cases of pituitary-dependent hyperadrenocorticism
(Cushing’s).
In cats, cabergoline, with or without a prostaglandin, may be useful
for pregnancy termination, particularly earlier in pregnancy.
Preliminary work has been done in psittacines (primarily
Cockatiels) for adjunctive treatment of reproductive-related disorders,
particularly persistent egg laying.
In humans, cabergoline is indicated for the treatment of disorders
associated with hyperprolactenemia or the treatment of Parkinson’s
disease.
in vitro
receptor binding studies have demonstrated that cabergoline has high in vitro selectivity and affinity for the subtype d2 of the dopamine receptor. in rat anterior pituitary cells, the concentration of cabergoline required to inhibit prl secretory activity by 50% were 0.1 nmol/l [1].
in vivo
in various animal models, cabergoline markedly reduced plasma prl levels in vivo after single or multiple doses, and the prl-lowering effects appeared 2 - 8 h after administration lasting for 72 h or longer. in addition, a single dose of cabergoline 0.6 mg/kg to rats, inhibited the serum levels of prl for 6 days significantly [1].
Drug interactions
Potentially hazardous interactions with other drugs
None known
IC 50
0.1 nm
Metabolism
Cabergoline is subject to first-pass metabolism and is
extensively metabolised to several metabolites that do not
appear to contribute to its pharmacological activityCabergoline is mainly eliminated via the faeces (72%); a
small proportion is excreted in the urine (18%).
references
[1] annamaria colao, gaetano lombardi & lucio annunziato. cabergoline. exp. opin. pharmacother. (2000) 1(3):555-574
Check Digit Verification of cas no
The CAS Registry Mumber 81409-90-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,1,4,0 and 9 respectively; the second part has 2 digits, 9 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 81409-90:
(7*8)+(6*1)+(5*4)+(4*0)+(3*9)+(2*9)+(1*0)=127
127 % 10 = 7
So 81409-90-7 is a valid CAS Registry Number.
InChI:InChI=1/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
81409-90-7Relevant articles and documents
New and efficient process for the preperation of cabergoline and its intermediates
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Page/Page column 12, (2008/12/08)
This invention relates to a new and efficient process for the production of dopamine agonists such as Cabergoline and the intermediates thereof.
New crystal form of cabergoline
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Page/Page column 7, (2008/12/07)
The present invention relates to a new needle-form crystalline cabergoline form L, its preparation from halogenated aromatic solvents and aliphatic hydrocarbons and its use in pharmaceutical composition.
PROCESS FOR THE PREPARATION OF CRYSTAL FORMS OF CABERGOLINE VIA NOVEL STABLE SOLVATES OF CABERGOLINE
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Page/Page column 10, (2008/12/05)
The present invention relates to a process for producing cabergoline crystal forms. The process comprises preparation of the desired solvate of cabergoline from a solution of cabergoline in chloroaromatic solvents. Afterwards cabergoline crystal form is prepared by recovery from a solvate of cabergoline by drying or with desolvating in a solvent media.
PROCESS FOR THE PREPARATION OF AMORPHOUS CABERGOLINE
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Page/Page column 4,5, (2008/12/07)
The present invention relates to processes for the preparation of amorphous cabergoline by agitated thin film drying or spray drying.
Production of Cabergoline and Novel Polymorphic Form Thereof
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Page/Page column 4; 1, (2008/06/13)
The present application relates to a novel polymorphic form of cabergoline comprising cabergoline and t-amyl methyl ether, designated Form TAME cabergoline, together with a novel method of producing cabergoline.
IMPROVED PROCESS FOR MAKING CABERGOLINE
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Page/Page column 13, (2010/11/23)
The invention relates to a process for preparing cabergoline of formula (1).
Preparation of cabergoline
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Page/Page column 2, (2010/02/14)
The present invention discloses a method for preparing cabergoline form I by combining cabergoline and a solvent comprising ethylbenzene to form a solvate and obtaining form I from the solvate. Also disclosed in a method for preparing cabergoline form I by combining cabergoline and a first solvent to form a solution and additionally including a second solvent to the solution, followed by crystallization to form cabergoline form I. Further disclosed is a solvate form of cabergoline comprising cabergoline and ethylbenzene and, optionally, n-heptane.
NOVEL PROCESS FOR PRODUCTION OF CABERGOLINE
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Page/Page column 22, (2008/06/13)
A process for preparing cabergoline (I) from ergoline-8β-carboxylic acid ester (XIII) comprising the following steps. (a) reacting an ergoline-8β-carboxylic acid ester of formula (XIII), wherein R1 represents a C1-4 alkyl group, in the presence of a catalyst (i) with a compound of formula (XIV), X-COOR2 (XIV) wherein R2 is an optionally substituted straight or branched C1-6 alkyl group, X represents a bromine or chlorine atom, or (ii) with a compound of formula (XV), O(COOR2)2 (XV) wherein R2 is a group as defined above; (b) reacting the obtained carbamate derivative of formula (XVI) with 3-(dimethylamino)-propylamine (DMAPA) in the presence of a catalyst; (c) reacting the obtained ergoline-8β-carboxamide derivative of formula (XVII) with ethyl isocyanate (EtNCO) in the presence of ligand(s) and Ib and IIb metal group salt catalysts; (d) reacting the obtained protected N-acylurea derivative of formula (XVIII) with a strong aqueous inorganic acid (aq./acid); (e) reacting the obtained secondary amine (XIX) with an electrophyl allyl alcohol derivative in the presence of a palladium or nickel containing catalyst and optionally in the presence of ligand(s) to form cabergoline (I). The intermediates of (XVI), (XVII), (XVIII) and (XIX) are novel. The polymorphic amorphous form of Cabergoline (I) and the production thereof.
Forms of cabergoline
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Page 8-9, (2010/02/08)
The invention provides methods for preparing amorphous physical form of cabergoline, and solvate form A of cabergoline useful in the preparation of the first mentioned physical form. A method for treating a prolactin disorder with medicaments prepared from amorphous physical form of cabergoline and solvate form A of cabergoline is also disclosed.
POLYMORPHS OF CABERGOLINE
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Page 33,34, (2008/06/13)
Provided are new crystalline Forms, VIII, IX, XI, XII, XIV, XV, XVI, XVII, and XVIII of cabergoline. Also provided are novel processes for preparation of cabergoline Form I, Form II, Form VII, and amorphous cabergoline.
