Bromocriptine

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Bromocriptine
Bromocriptine2DACS.svg
Bromocriptine3DanJ.gif
Systematic (IUPAC) name
(5′α)-2-bromo-12′-hydroxy-5′-(2-methylpropyl)-3′,6′,18-trioxo-2′-(propan-2-yl)ergotaman
Clinical data
Trade names Parlodel, Brotin
AHFS/Drugs.com monograph,International Drug Names
MedlinePlus a682079
Pregnancy cat. A (AU) B (US)
Legal status Prescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routes oral, intravenous
Pharmacokinetic data
Bioavailability 28% of oral dose absorbed
Metabolism Extensively liver-mediated
Half-life 12-14 hours
Excretion 85% bile (faeces), 2.5-5.5% urine
Identifiers
CAS number 25614-03-3 YesY
ATC code G02CB01 N04BC01
PubChem CID 31101
IUPHAR ligand 35
DrugBank DB01200
ChemSpider 28858 YesY
UNII 3A64E3G5ZO YesY
KEGG D03165 YesY
ChEBI CHEBI:3181 YesY
ChEMBL CHEMBL493 YesY
Chemical data
Formula C32H40BrN5O5 
Mol. mass 654.595
 YesY (what is this?)  (verify)

Bromocriptine (INN; trade names Parlodel, Cycloset, Brotin (Pakistan)), an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease (PD), hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.

Indications[edit]

Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly may all be caused by pituitary problems, such as hyperprolactinaemia, and therefore, these problems may be treated with this drug. Bromocriptine has completely treated gestational macromastia eliminating the need for reduction surgery, in a recent case.[1]Since the late 1980s it has been used, off-label, to reduce the symptoms of cocaine withdrawal.[2][3] In 2009, bromocriptine mesylate was approved by the FDA for treatment of type 2 diabetes under the trade name Cycloset (VeroScience). It is currently unknown how this drug improves glycemic control, but it has been shown to reduce HbA1c by ~0.5 percentage points.[4]

Pharmacology[edit]

Bromocriptine is a potent agonist at dopamine D2 receptors[5] and various serotonin receptors. It also inhibits the release of glutamate, by reversing the glutamate GLT1 transporter.[6]

Bromocriptine agonizes the following monoamine receptors:[7]

  • Dopamine D1 family
    • D1 (Ki=682 nM)
    • D5 (Ki=496 nM)
  • Dopamine D2 family
    • D2 (Ki=2.96 nM)
    • D3 (Ki=5.42 nM)
    • D4 (Ki=328 nM)
  • Serotonin 5-HT
  • Adrenergic α family
  • Adrenergic β family
    • β1 (Ki=589 nM)
    • β2 (Ki=741 nM)

Side effects[edit]

Most frequent side effects are nausea, orthostatic hypotension, headaches, and vomiting through stimulation of the brainstem vomiting centre.[8] Bromocriptine can cause worsening of liver problems. Vasospasms with serious consequences such as myocardial infarction and stroke that have been reported in connection with the puerperium, appear to be extremely rare events.[9] Peripheral vasospasm (of the fingers or toes) can cause Raynaud's Phenomenon. Bromocriptine use has been anecdotally associated with causing or worsening psychotic symptoms (its mechanism is in opposition of most antipsychotics, whose mechanisms generally block dopamine).[10] Pulmonary fibrosis has been reported when bromocriptine was used in high doses for the treatment of Parkinson's disease.[11]

Use to suppress milk production after childbirth was reviewed in 2014 and it was concluded that in this context a causal association with serious cardiovascular, neurological or psychiatric events could not be excluded with an overall incidence rate estimated to range between 0.005% and 0.04%. Additional safety precautions and stricter prescribing rules were suggested based on the data.[12][13]

Chemistry[edit]

Like all ergopeptides, bromocriptine is a cyclol; two peptide groups of its tripeptide moiety are crosslinked, forming the >N-C(OH)< juncture between the two rings with the amide functionality.

Bromocriptine, 2-bromoergocriptine, is a semisynthetic derivative of a natural ergot alkaloid, ergocriptin (a derivative of lysergic acid), which is synthesized by bromination of ergocriptin using N-bromosuccinimide.

Bromocriptine synthesis.png

See also[edit]

References[edit]

  1. ^ Ezem, Osuagwu, Opara (February 2011). "Gestational gigantomastia with complete resolution in a Nigerian woman". BMJ 2011. doi:10.1136/bcr.01.2010.2632. PMC 3062818. PMID 22707463. 
  2. ^ AJ Giannini, P Baumgartel, LR DiMarzio. Bromocriptine therapy in cocaine withdrawal. J. Clinical Pharmacology. 27: 267-270,1987.
  3. ^ FS Tenant, AA Sagherian. Double-blind comparison of amantadine hydrochloride and bromocriptine mesylate for ambulatory withdrawal from cocaine dependence. Archives of General Medicine. 147: 109-112,1987.
  4. ^ Pijl H, Ohashi S, Matsuda M, et al. (August 2000). "Bromocriptine: a novel approach to the treatment of type 2 diabetes". Diabetes Care 23 (8): 1154–61. doi:10.2337/diacare.23.8.1154. PMID 10937514. 
  5. ^ De Leeuw Van Weenen, J. E.; Parlevliet, E. T.; Maechler, P.; Havekes, L. M.; Romijn, J. A.; Ouwens, D. M.; Pijl, H.; Guigas, B. (2010). "The dopamine receptor D2 agonist bromocriptine inhibits glucose-stimulated insulin secretion by direct activation of the α2-adrenergic receptors in beta cells". Biochemical Pharmacology 79 (12): 1827. doi:10.1016/j.bcp.2010.01.029. PMID 20138024.  edit
  6. ^ "ScienceDirect - European Journal of Pharmacology : Bromocriptine, an ergot alkaloid, inhibits excitatory amino acid release mediated by glutamate transporter reversal". Retrieved 2010-08-31. 
  7. ^ National Institute ofMental Health. PDSD Ki Database (Internet) [cited 2013 Jul 24]. ChapelHill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php
  8. ^ Weil, C. (1986). "The safety of bromocriptine in long-term use: a review of the literature". Current medical research and opinion 10 (1): 25–51. doi:10.1185/03007998609111089. PMID 3516579.  edit
  9. ^ Iffy, L; McArdle, JJ; Ganesh, V; Hopp, L (1996). "Bromocriptine related atypical vascular accidents postpartum identified through medicolegal reviews". Medicine and law 15 (1): 127–34. PMID 8691994.  edit
  10. ^ Boyd, A. (1995). "Bromocriptine and psychosis: a literature review". The Psychiatric quarterly 66 (1): 87–95. doi:10.1007/BF02238717. PMID 7701022.  edit
  11. ^ Todman, D.; Oliver, W.; Edwards, R. (1990). "Pleuropulmonary fibrosis due to bromocriptine treatment for Parkinson's disease". Clinical and experimental neurology 27: 79–82. PMID 2129961.  edit
  12. ^ EMA Statement "CMDh endorses restricted use of bromocriptine for stopping breast milk production"
  13. ^ http://m.aerzteblatt.de/news/59857.htm "EMA rät vom Abstillmittel Bromocriptin ab", article in Ärzteblatt

External links[edit]