Definition
Description
Top Gene Interactions
Related Pathways
General Information
- 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
- Uses/Sources: 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)
- Health Effects: 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)
- Symptoms: 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: 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)
- Route of Exposure: 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.
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Cytochrome P450 3A4 5-hydroxytryptamine receptor 2A 5-hydroxytryptamine receptor 2C 5-hydroxytryptamine receptor 1A Alpha-1A adrenergic receptor Alpha-2A adrenergic receptor 5-hydroxytryptamine receptor 7 5-hydroxytryptamine receptor 1D D(1A) dopamine receptor Alpha-1B adrenergic receptor Alpha-1D adrenergic receptor Alpha-2B adrenergic receptor D(1B) dopamine receptor Beta-1 adrenergic receptor 5-hydroxytryptamine receptor 6 Alpha-2C adrenergic receptor |
9686407 19509219 18703043 18996971 17198380 12388666 9057850 18691132 8522988 20138024 10641988 19128860 1826762 |
|
D(2) dopamine receptor | Bromocriptine acts by directly stimulating the dopamine receptors in the corpus striatum. (A2311, A2312, A2313, A2314, A2315, A365, A2941) |
10721819 10626749 10455328 9057850 12010185 11752352 11444429 12753422 |
Adenylate cyclase type 7 | Bromocriptine inhibits the activity of adenylate cyclase. (A2319, A2320, A2321, A2322, A2323) |
16410672 10188934 10072194 12742521 11002291 |
Cytochrome P450 3A3 | Bromocriptine inhibits the metabolic activities of CYP3A3. (A2308, A2309, A2310) |
16566594 9868741 17573349 |
D(3) dopamine receptor D(4) dopamine receptor |
Bromocriptine acts by directly stimulating the dopamine receptors in the corpus striatum. (A2941) |
9057850 10455328 |
Cyclic AMP-responsive element-binding protein 1 | Bromocriptine induces CREB DNA-binding activities. (A2316, A2317, A2318) |
11923475 8726116 10596389 |
5-hydroxytryptamine receptor 2B 5-hydroxytryptamine receptor 1B |
Agonism of 5-HT2B and 5-HT1B receptors is believed to be responsible for the fibrotic reactions and cardiac valvular disease associated with bromocriptine use. (A2933) |
12388666 18691132 |
Somatostatin | Bromocriptine inhibits somatostatin. (A2324, A2325, A2326) |
11385964 9510128 11291426 |
Bromocriptine Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Radiation Injuries, Experimental | 20.44 |
|
Infertility, Female | 19.92 |
|
Diabetes Mellitus, Experimental | 17.63 |
|
Prostatic Neoplasms | 17.42 |
|
Parkinson's disease | 17.21 |
|
Liver Cirrhosis, Experimental | 16.02 |
|
Mammary Neoplasms, Experimental | 15.49 |
|
Cocaine dependence | 14.57 |
|
Diabetes Mellitus, Type 2 | 14.38 |
|
Status Epilepticus | 14.36 |
|
Endometrial neoplasm | 14.13 |
|
Turner Syndrome | 14.04 |
|
Alzheimer's Disease | 13.49 |
|
Obesity | 13.45 |
|
Lung Neoplasms | 13.25 |
|
Heroin Dependence | 13.18 |
|
Adenocarcinoma | 13.03 |
|
Nerve Degeneration | 12.81 |
|
Hepatoblastoma | 11.75 |
|
Neoplasm Metastasis | 11.4 |
|