Bromocriptine
 |
|
 |
|
| 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 category |
|
| Legal status | |
| Routes of administration |
oral, intravenous |
| Pharmacokinetic data | |
| Bioavailability | 28% of oral dose absorbed |
| Metabolism | Extensively liver-mediated |
| Biological half-life | 12-14 hours |
| Excretion | 85% bile (faeces), 2.5-5.5% urine |
| Identifiers | |
| CAS Number | 25614-03-3  |
| ATC code | G02CB01 (WHO) N04BC01 |
| PubChem | CID: 31101 |
| IUPHAR/BPS | 35 |
| DrugBank | DB01200 |
| ChemSpider | 28858 |
| UNII | 3A64E3G5ZO |
| KEGG | D03165 |
| ChEBI | CHEBI:3181 |
| ChEMBL | CHEMBL493 |
| Synonyms | 2-Bromoergocriptine |
| Chemical data | |
| Formula | C32H40BrN5O5 |
| Molecular mass | 654.595 g/mol |
|
|
|
|
| (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.
Contents
Indications
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] It has also been used in treating nonpuerperal mastitis.[2] Since the late 1980s it has been used, off-label, to reduce the symptoms of cocaine withdrawal.[3][4] 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.[5]
Pharmacology
Bromocriptine is a potent agonist at dopamine D2 receptors[6] and various serotonin receptors. It also inhibits the release of glutamate, by reversing the glutamate GLT1 transporter.[7]
Bromocriptine agonizes the following monoamine receptors:[8]
- Dopamine D1 family
- Dopamine D2 family
- Serotonin 5-HT
- Adrenergic α family
- Adrenergic β family
Side effects
Most frequent side effects are nausea, orthostatic hypotension, headaches, and vomiting through stimulation of the brainstem vomiting centre.[9] 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.[10] 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).[11] Pulmonary fibrosis has been reported when bromocriptine was used in high doses for the treatment of Parkinson's disease.[12]
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.[13][14]
Chemistry
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 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.[15][16]
See also
References
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ AJ Giannini, P Baumgartel, LR DiMarzio. Bromocriptine therapy in cocaine withdrawal. J. Clinical Pharmacology. 27: 267-270,1987.
- ↑ 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.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ 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
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ EMA Statement "CMDh endorses restricted use of bromocriptine for stopping breast milk production"
- ↑ http://m.aerzteblatt.de/news/59857.htm "EMA rät vom Abstillmittel Bromocriptin ab", article in Ärzteblatt
- ↑ E. Fluckiger, A. Hofmann, U.S. Patent 3,752,814 (1973)
- ↑ A. Hofmann, E. Flueckiger, DE 1926045 (1969)
