3059
T3D3017
Bromocriptine
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.
25614-03-3
31101
C32H40BrN5O5
653.221280
White powder.
215-218°C
8.58e-02 g/L
Oral (L1934). 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.
The dopamine D<sub>2</sub> receptor is a 7-transmembrane G-protein coupled receptor associated with G<sub>i</sub> proteins. In lactotrophs, stimulation of dopamine D<sub>2</sub> receptor causes inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP3-dependent release of Ca<sup>2+</sup> 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 D<sub>2</sub> receptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders.
Ergoline alkaloids have been shown to have the significant affinity towards the 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and alpha-adrenergic receptors. This can result in a number of different effects, including vasoconstriction, convulsions, and hallucinations. Bromocriptine acts by directly stimulating the dopamine receptors in the corpus striatum. (A2914, A2915, A2916, A2941)
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
No indication of carcinogenicity to humans (not listed by IARC).
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.
Bromocriptine is a semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used in the treatment of pituitary tumors, Parkinson's disease (PD),Hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes. Ergoline alkaloids occurs in various species of vines of the Convolvulaceae (morning glory) family and in some species of lower fungi. (L1918, L1934)
A slight hypotensive effect may accompany bromocriptine treatment. Few cases of cerebrospinal fluid rhinorrhea have been reported in patients receiving bromocriptine for treatment of large prolactinomas. Bromocriptine use has been associated with causing or worsening psychotic symptoms and fibrosis of multiple organs. Ingestion of ergoline alkaloids is known to cause the disease ergotism. Ergotism occurs in two forms, gangrenous and convulsive, likely depending on the different kinds and amounts of ergoline alkaloids present. (A2913, L1827, L1934)
Side effects of bromocriptine include nausea, headache, dizziness, fatigue, lightheadedness, vomiting, abdominal cramps, nasal congestion, constipation, diarrhea and drowsiness. Convulsive ergotism can cause painful seizures and spasms, diarrhea, paresthesias, itching, headaches, nausea and vomiting. Usually the gastrointestinal effects precede the central nervous system effects. As well as seizures there can be hallucinations and mental effects including mania or psychosis. Gangrenous ergotism causes dry gangrene as a result of vasoconstriction induced in the more poorly vascularized distal structures, such as the fingers and toes. Symptoms include desquamation, weak periphery pulse, loss of peripheral sensation, edema and ultimately the death and loss of affected tissues. (L1920, L1827)
Treatment of overdose consists of removal of the drug by emesis (if conscious), gastric lavage, activated charcoal, or saline catharsis. Careful supervision and recording of fluid intake and output is essential. Hypotension should be treated by placing the patient in the Trendelenburg position and administering I.V. fluids. If satisfactory relief of hypotension cannot be achieved by using the above measures to their fullest extent, vasopressors should be considered. (L1827)
2009-07-21T20:28:37Z
2014-12-24T20:25:55Z
Bromocriptine
C06856
3181
Bromocriptine
DB01200
08Y
true
[H][C@@]12CCCN1C(=O)[C@]([H])(CC(C)C)N1C(=O)[C@@](O[C@@]21O)(N=C(O)[C@@]1([H])CN(C)[C@]2([H])CC3=C(Br)NC4=CC=CC(=C34)C2=C1)C(C)C
C32H40BrN5O5
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
InChIKey=OZVBMTJYIDMWIL-AYFBDAFISA-N
654.595
653.221282062
Exogenous
Solid
3.5
HMDB15331
CHEMBL493
28858
<p>Luigi Moro, Achille Fiori, Alberto Natali, “Processes for the preparation of pharmaceutical compositions containing bromocriptine having high stability and related products.” U.S. Patent US5066495, issued May, 1988.</p>