QuickView for Bromocriptine (compound)

Summary
General Info

PubChem

PubChem Compound 2443

Name:	Bromocriptine
PubChem Compound ID:	2443
Description:	A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.
Molecular formula:	C₃₂H₄₀BrN₅O₅
Molecular weight:	654.595 g/mol
Synonyms:	Ergotaman-3',6',18-trione, 2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)-, (5'.alpha.)-; Bromocriptine

DrugBank

Identification

Name:	Bromocriptine
Name (isomeric):	DB01200
Drug Type:	small molecule
Description:	A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.
Synonyms:	Bromocryptine; Bromocriptinum [INN-Latin]; Bromoergocryptine; Bromergocryptine; Bromocryptine Mesylate; Bromoergocriptine; Bromocriptine Methanesulfonate; Bromocriptina [INN-Spanish]; Bromocriptine Mesylate; Bromocriptin
Brand:	Bagren, Apo-Bromocriptine, Alti-Bromocriptine, Parlodel Snaptabs, Parlodel, Pravidel, Ergoset
Category:	Antidyskinetics, Hormone Antagonists, Antiparkinson Agents, Dopamine Agonists
CAS number:	25614-03-3

Pharmacology

Indication:	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.
Pharmacology:	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 dopaminergi... show more » 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-HT_1A, 5-HT_2A, 5-HT_1B, and 5-HT_2C receptors, antagonist activity on α_2A-adrenergic, α_2C, α_2B, and dopamine D₁ receptors, partial agonist activity at receptor 5-HT_2B, 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-HT_2A 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-HT_1B and 5-HT_2B receptors. show less «
Mechanism of Action:	The dopamine D₂ receptor is a 7-transmembrane G-protein coupled receptor associated with G_i 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 sto... show more » The dopamine D₂ receptor is a 7-transmembrane G-protein coupled receptor associated with G_i 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. show less «
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
Biotransformation:	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
Toxicity:	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.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Avoid alcohol.

Take with food to reduce irritation.

Drug interaction:

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.
Perphenazine	The phenothiazine decreases the effect of bromocriptine
Mesoridazine	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.
Tramadol	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

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.
Perphenazine	The phenothiazine decreases the effect of bromocriptine
Mesoridazine	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.
Tramadol	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Methdilazine	The phenothiazine decreases the effect of bromocriptine
Trimipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Chlorpromazine	The phenothiazine decreases the effect of bromocriptine
Acetophenazine	The phenothiazine decreases the effect of bromocriptine
Promazine	The phenothiazine decreases the effect of bromocriptine
Tranylcypromine	Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Phenylpropanolamine	The sympathomimetic, phenylpropanolamine, increases the toxicity of bromocriptine.
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Propiomazine	The phenothiazine decreases the effect of bromocriptine
Voriconazole	Voriconazole may increase the serum concentration of bromocriptine likely by decreasing its metabolism. Concomitant therapy is contraindicated.
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Fluphenazine	The phenothiazine decreases the effect of bromocriptine
Trifluoperazine	The phenothiazine decreases the effect of bromocriptine
Methotrimeprazine	The phenothiazine decreases the effect of bromocriptine
Josamycin	Erythromycin increases serum levels of bromocriptine
Erythromycin	Erythromycin increases serum levels of bromocriptine
Pseudoephedrine	The sympathomimetic, pseudoephedrine, increases the toxicity of bromocriptine.
Ethopropazine	The phenothiazine decreases the effect of bromocriptine
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.
Ziprasidone	The atypical antipsychotic, ziprasidone, may antagonize the effect of the dopamine agonist, bromocriptine. Consider alternate therapy or monitor for worsening of movement disorder.
Triflupromazine	The phenothiazine decreases the effect of bromocriptine
Trimeprazine	The phenothiazine decreases the effect of bromocriptine
Thiethylperazine	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.
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.
Tipranavir	Tipranavir may increase the plasma concentration of Bromocriptine. Concomitant therapy should be avoided.
Thioridazine	The phenothiazine decreases the effect of bromocriptine
Promethazine	The phenothiazine decreases the effect of bromocriptine
Prochlorperazine	The phenothiazine decreases the effect 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.