Tìm theo
Bromocriptine
Các tên gọi khác (14 ) :
  • (5'alpha)-2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)-3',6',18-trioxoergotaman
  • (5'alpha)-2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)ergotaman-3',6',18-trione
  • (5'alpha)-2-bromo-12'-hydroxy-5'-isobutyl-2'-isopropyl-3',6',18-trioxoergotaman
  • 2-Bromo-alpha-ergocryptine
  • 2-Bromo-alpha-ergokryptin
  • 2-Bromo-alpha-ergokryptine
  • 2-bromo-α-ergocryptine
  • 2-bromo-α-ergokryptin
  • 2-bromo-α-ergokryptine
  • Bromocriptina
  • Bromocriptinum
  • Bromocryptine
  • Bromoergocriptine
  • Bromoergocryptine
Thuốc hormon và kháng hormon
Thuốc Gốc
Small Molecule
CAS: 25614-03-3
ATC: G02CB01, N04BC01
ĐG : Amerisource Health Services Corp. , http://www.amerisourcebergen.com
CTHH: C32H40BrN5O5
PTK: 654.595
Bromocriptine mesylate is a semisynthetic ergot alkaloid derivative with potent dopaminergic activity. It is indicated for the management of signs and symptoms of Parkinsonian Syndrome. Bromocriptine also inhibits prolactin secretion and may be used to treat dysfunctions associated with hyperprolactinemia. It also causes sustained suppression of somatotropin (growth hormone) secretion in some patients with acromegaly. Bromocriptine has been associated with pulmonary fibrosis.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C32H40BrN5O5
Phân tử khối
654.595
Monoisotopic mass
653.221282062
InChI
InChI=1S/C32H40BrN5O5/c1-16(2)12-24-29(40)37-11-7-10-25(37)32(42)38(24)30(41)31(43-32,17(3)4)35-28(39)18-13-20-19-8-6-9-22-26(19)21(27(33)34-22)14-23(20)36(5)15-18/h6,8-9,13,16-18,23-25,34,42H,7,10-12,14-15H2,1-5H3,(H,35,39)/t18-,23-,24+,25+,31-,32+/m1/s1
InChI Key
InChIKey=OZVBMTJYIDMWIL-AYFBDAFISA-N
IUPAC Name
(4R,7R)-10-bromo-N-[(1S,2S,4R,7S)-2-hydroxy-7-(2-methylpropyl)-5,8-dioxo-4-(propan-2-yl)-3-oxa-6,9-diazatricyclo[7.3.0.0^{2,6}]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide
Traditional IUPAC Name
bromocriptine
SMILES
[H][C@@]12CCCN1C(=O)[C@H](CC(C)C)N1C(=O)[C@](NC(=O)[C@H]3CN(C)[C@]4([H])CC5=C(Br)NC6=CC=CC(=C56)C4=C3)(O[C@@]21O)C(C)C
Độ tan chảy
215-218
Độ hòa tan
8.58e-02 g/l
logP
3.5
logS
-3.9
pKa (strongest acidic)
9.68
pKa (Strongest Basic)
6.71
PSA
118.21 Å2
Refractivity
165.51 m3·mol-1
Polarizability
66.44 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
6
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
7
Bioavailability
1
Dược Lực Học : Bromocriptine 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-receptors. It also exhibits agonist activity (in order of decreasing binding affinity) on 5-hydroxytryptamine (5-HT)1D, dopamine D3, 5-HT1A, 5-HT2A, 5-HT1B, and 5-HT2C receptors, antagonist activity on α2A-adrenergic, α2C, α2B, and dopamine D1 receptors, partial agonist activity at receptor 5-HT2B, and inactivates dopamine D4 and 5-HT7 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 making bromocriptine an effective agent for treating disorders associated with hypersecretion of prolactin. Pulmonary fibrosis may be associated bromocriptine’s agonist activity at 5-HT1B and 5-HT2B receptors.
Cơ Chế Tác Dụng : Bromocriptine mesylate is a semisynthetic ergot alkaloid derivative with potent dopaminergic activity. It is indicated for the management of signs and symptoms of Parkinsonian Syndrome. Bromocriptine also inhibits prolactin secretion and may be used to treat dysfunctions associated with hyperprolactinemia. It also causes sustained suppression of somatotropin (growth hormone) secretion in some patients with acromegaly. Bromocriptine has been associated with pulmonary fibrosis. The dopamine D2 receptor is a 7-transmembrane G-protein coupled receptor associated with Gi proteins. In lactotrophs, stimulation of dopamine D2 receptor 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.
Dược Động Học :
▧ Absorption :
Approximately 28% of the oral dose is absorbed; however due to a substantial first pass effect, only 6% of the oral dose reaches the systemic circulation unchanged. Bromocriptine and its metabolites appear in the blood as early as 10 minutes following oral administration and peak plasma concentration are reached within 1-1.5 hours. Serum prolactin may be decreased within 2 hours or oral administration with a maximal effect achieved after 8 hours. Growth hormone concentrations in patients with acromegaly is reduced within 1-2 hours with a single oral dose of 2.5 mg and decreased growth hormone concentrations persist for at least 4-5 hours.
▧ Protein binding :
90-96% bound to serum albumin
▧ Metabolism :
Completely metabolized by the liver, primarily by hydrolysis of the amide bond to produce lysergic acid and a peptide fragment, both inactive and non-toxic. Bromocriptine is metabolized by cytochrome P450 3A4 and excreted primarily in the feces via biliary secretion.
▧ Route of Elimination :
Parent drug and metabolites are almost completely excreted via the liver, and only 6% eliminated via the kidney.
▧ Half Life :
2-8 hours
Độc Tính : Symptoms of overdosage include nausea, vomiting, and severe hypotension. The most common adverse effects include nausea, headache, vertigo, constipation, light-headedness, abdominal cramps, nasal congestion, diarrhea, and hypotension.
Chỉ Định : For the treatment of galactorrhea due to hyperprolactinemia, prolactin-dependent menstrual disorders and infertility, prolactin-secreting adenomas, prolactin-dependent male hypogonadism, as adjunct therapy to surgery or radiotherapy for acromegaly or as monotherapy is special cases, as monotherapy in early Parksinsonian Syndrome or as an adjunct with levodopa in advanced cases with motor complications. Bromocriptine has also been used off-label to treat restless legs syndrome and neuroleptic malignant syndrome.
Tương Tác Thuốc :
  • Acetophenazine The phenothiazine decreases the effect of bromocriptine
  • Alimemazine The phenothiazine decreases the effect of bromocriptine
  • Chlorpromazine The phenothiazine decreases the effect of bromocriptine
  • Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Erythromycin Erythromycin increases serum levels of bromocriptine
  • Ethopropazine The phenothiazine decreases the effect of bromocriptine
  • Fluphenazine The phenothiazine decreases the effect of bromocriptine
  • Josamycin Erythromycin increases serum levels of bromocriptine
  • Mesoridazine The phenothiazine decreases the effect of bromocriptine
  • Methdilazine The phenothiazine decreases the effect of bromocriptine
  • Methotrimeprazine The phenothiazine decreases the effect of bromocriptine
  • Paliperidone The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, bromocriptine. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.
  • Perphenazine The phenothiazine decreases the effect of bromocriptine
  • Phenylpropanolamine The sympathomimetic, phenylpropanolamine, increases the toxicity of bromocriptine.
  • Prochlorperazine The phenothiazine decreases the effect of bromocriptine
  • Promazine The phenothiazine decreases the effect of bromocriptine
  • Promethazine The phenothiazine decreases the effect of bromocriptine
  • Propiomazine The phenothiazine decreases the effect of bromocriptine
  • Pseudoephedrine The sympathomimetic, pseudoephedrine, increases the toxicity of bromocriptine.
  • Tacrolimus Bromocriptine may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Bromocriptine therapy is initiated, discontinued or altered.
  • Telithromycin Telithromycin may reduce clearance of Bromocriptine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Bromocriptine if Telithromycin is initiated, discontinued or dose changed.
  • Thiethylperazine The phenothiazine decreases the effect of bromocriptine
  • Thioridazine The phenothiazine decreases the effect of bromocriptine
  • Thiothixene Thiothixene may antaonize the effects of the anti-Parkinsonian agent, Bromocriptine. Consider alternate therapy or monitor for decreased effects of both agents.
  • Tipranavir Tipranavir may increase the plasma concentration of Bromocriptine. Concomitant therapy should be avoided.
  • 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.
  • Trifluoperazine The phenothiazine decreases the effect of bromocriptine
  • Triflupromazine The phenothiazine decreases the effect of bromocriptine
  • 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 bromocriptine likely by decreasing its metabolism. Concomitant therapy is contraindicated.
  • Ziprasidone The atypical antipsychotic, ziprasidone, may antagonize the effect of the dopamine agonist, bromocriptine. Consider alternate therapy or monitor for worsening of movement disorder.
  • Zolmitriptan Concomitant use of the serotonin 5-HT1D receptor agonist, zolmitriptan, and the ergot derivative, bromocriptine, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated. Use of two serotonin modulators, such as zolmitriptan and bromocriptine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
  • Zuclopenthixol Antagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and bromocriptine, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
Liều Lượng & Cách Dùng : Capsule - Oral - 5 mg
Tablet - Oral - 2.5 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Apotex
    Sản phẩm biệt dược : Apo-Bromocriptine
  • Công ty : Serono (Brazil)
    Sản phẩm biệt dược : Bagren
  • Công ty :
    Sản phẩm biệt dược : CYCLOSET
  • Công ty :
    Sản phẩm biệt dược : Ergoset
  • Công ty : Novartis
    Sản phẩm biệt dược : Parlodel
  • Công ty : Novartis
    Sản phẩm biệt dược : Parlodel Snaptabs
  • Sản phẩm biệt dược : Pravidel
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01200
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=31101
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505504
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C06856
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D03165
ChemSpider
http://www.chemspider.com/Chemical-Structure.28858.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0078-0017-15
PharmGKB
http://www.pharmgkb.org/drug/PA448671
Wikipedia
http://en.wikipedia.org/wiki/Bromocriptine
RxList
http://www.rxlist.com/cgi/generic3/bromocriptine.htm
Drugs.com
http://www.drugs.com/cdi/bromocriptine.html
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