Tìm theo
Cabergoline
Các tên gọi khác (8 ) :
  • (8beta)-N-[3-(dimethylamino)Propyl]-N-[(ethylamino)carbonyl]-6-(2-propenyl)-ergoline-8-carboxamide
  • (8R)-6-Allyl-N-[3-(dimethylamino)propyl]-N-(ethylcarbamoyl)ergoline-8-carboxamide
  • 1-((6-Allylergolin-8beta-yl)carbonyl)-1-(3-(dimethylamino)propyl)-3-ethylurea
  • 1-[(6-Allylergoline-8beta-yl)carbonyl]-1-[3-(dimethylamino)propyl]-3-ethylurea
  • 1-Ethyl-3-(3'-dimethylamionpropyl)-2-(6'-allylergoline-8'beta-carbonyl)urea
  • Cabergolina
  • Cabergoline
  • Cabergolinum
Thuốc điều trị ung thư
Thuốc Gốc
Small Molecule
CAS: 81409-90-7
ATC: G02CB03, N04BC06
ĐG : Amerisource Health Services Corp. , http://www.amerisourcebergen.com
CTHH: C26H37N5O2
PTK: 451.6043
Cabergoline, an ergot derivative, is a long-acting dopamine agonist and prolactin inhibitor. It is used to treat hyperprolactinemic disorders and Parkinsonian Syndrome. Cabergoline possesses potent agonist activity on dopamine D2 receptors.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C26H37N5O2
Phân tử khối
451.6043
Monoisotopic mass
451.294725453
InChI
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
InChI Key
InChIKey=KORNTPPJEAJQIU-KJXAQDMKSA-N
IUPAC Name
1-[3-(dimethylamino)propyl]-3-ethyl-1-{[(2R,4R,7R)-6-(prop-2-en-1-yl)-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),9,12,14-tetraen-4-yl]carbonyl}urea
Traditional IUPAC Name
cabergoline
SMILES
[H][C@@]12CC3=CNC4=CC=CC(=C34)[C@@]1([H])C[C@H](CN2CC=C)C(=O)N(CCCN(C)C)C(=O)NCC
Độ tan chảy
102-104 °C
Độ hòa tan
Insoluble
logP
2.6
logS
-3.9
pKa (strongest acidic)
15.25
pKa (Strongest Basic)
9.32
PSA
71.68 Å2
Refractivity
133.5 m3·mol-1
Polarizability
52.5 Å3
Rotatable Bond Count
8
H Bond Acceptor Count
4
H Bond Donor Count
2
Physiological Charge
2
Number of Rings
4
Bioavailability
1
Rule of Five
true
MDDR-Like Rule
true
Dược Lực Học : Cabergoline stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1 and D5 subreceptors, which are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3 and D4 subreceptors, which are associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2 and D3 receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2 stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2 stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2- and D3-receptors. It also exhibits: agonist activity (in order of decreasing binding affinities) on 5-hydroxytryptamine (5-HT)2B, 5-HT2A, 5-HT1D, dopamine D4, 5-HT1A, dopamine D1, 5-HT1B and 5-HT2C receptors and antagonist activity on α2B, α2A, and α2C receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2A agonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion.
Cơ Chế Tác Dụng : Cabergoline, an ergot derivative, is a long-acting dopamine agonist and prolactin inhibitor. It is used to treat hyperprolactinemic disorders and Parkinsonian Syndrome. Cabergoline possesses potent agonist activity on dopamine D2 receptors. The dopamine D2 receptor is a 7-transmembrane G-protein coupled receptor associated with Gi proteins. In lactotrophs, stimulation of dopamine D2 causes inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP3-dependent release of Ca2+ from intracellular stores. Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gated calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p42/p44 MAPK and decreases MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition. Stimulation of dopamine D2 receptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders. Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D2 receptors. Receptor-binding studies indicate that cabergoline has low affinity for dopamine D1, α1,- and α2- adrenergic, and 5-HT1- and 5-HT2-serotonin receptors.
Dược Động Học :
▧ Absorption :
First-pass effect is seen, however the absolute bioavailability is unknown.
▧ Protein binding :
Moderately bound (40% to 42%) to human plasma proteins in a concentration-independent manner.
▧ Metabolism :
Hepatic. Cabergoline is extensively metabolized, predominately via hydrolysis of the acylurea bond of the urea moiety. Cytochrome P-450 mediated metabolism appears to be minimal. The main metabolite identified in urine is 6-allyl-8b-carboxy-ergoline (4-6% of dose). Three other metabolites were identified urine (less than 3% of dose).
▧ Route of Elimination :
After oral dosing of radioactive cabergoline to five healthy volunteers, approximately 22% and 60% of the dose was excreted within 20 days in the urine and feces, respectively. Less than 4% of the dose was excreted unchanged in the urine.
▧ Half Life :
The elimination half-life is estimated from urinary data of 12 healthy subjects to range between 63 to 69 hours.
▧ Clearance :
* renal cl=0,008 L/min * nonrenal cl=3.2 L/min
Độc Tính : Overdosage might be expected to produce nasal congestion, syncope, or hallucinations.
Chỉ Định : For the treatment of hyperprolactinemic disorders, either idiopathic or due to prolactinoma (prolactin-secreting adenomas). May also be used to manage symptoms of Parkinsonian Syndrome as monotherapy during initial symptomatic management or as an adjunct to levodopa therapy during advanced stages of disease.
Tương Tác Thuốc :
  • Erythromycin Erythromycin increases serum levels and toxicity of cabergoline
  • Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
  • Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Voriconazole Voriconazole may increase the serum concentration of cabergoline likely by decreasing its metabolism. Concomitant therapy is contraindicated.
  • Zolmitriptan Concomitant use of the serotonin 5-HT1D receptor agonist, zolmitriptan, and the ergot derivative, carbergoline, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated. Use of two serotonin modulators, such as zolmitriptan and carbergoline, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Liều Lượng & Cách Dùng : Tablet - Oral - 0.5 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Pfizer
    Sản phẩm biệt dược : Cabaser
  • Công ty : Pfizer
    Sản phẩm biệt dược : Dostinex
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00248
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=54746
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508571
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C08187
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00987
ChemSpider
http://www.chemspider.com/Chemical-Structure.49452.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/49884-673-14
PharmGKB
http://www.pharmgkb.org/drug/PA448708
Wikipedia
http://en.wikipedia.org/wiki/Cabergoline
RxList
http://www.rxlist.com/cgi/generic/cabergoline.htm
Drugs.com
http://www.drugs.com/cdi/cabergoline.html
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