ContaminantDB: Bromocriptine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (25)XML

Record Information

Version

1.0

Creation Date

2009-07-21 20:28:37 UTC

Update Date

2026-05-14 16:58:42 UTC

Accession Number

CHEM002374

Identification

Common Name

Bromocriptine

Class

Small Molecule

Description

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.

Contaminant Sources

HMDB Contaminants - Urine
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Amide
Amine
Antidyskinetic
Antiparkinson Agent
Bromide Compound
Dopamine Agonist
Drug
Ether
Hormone Antagonist
Human Neurotoxin
Metabolite
Organic Compound
Organobromide
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(5'alpha)-2-Bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)-3',6',18-trioxoergotaman	ChEBI
(5'alpha)-2-Bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)ergotaman-3',6',18-trione	ChEBI
(5'alpha)-2-Bromo-12'-hydroxy-5'-isobutyl-2'-isopropyl-3',6',18-trioxoergotaman	ChEBI
2-Bromo-alpha-ergocryptine	ChEBI
2-Bromo-alpha-ergokryptin	ChEBI
2-Bromo-alpha-ergokryptine	ChEBI
Bromocriptinum	ChEBI
Bromocryptine	ChEBI
Bromoergocriptine	ChEBI
(5'a)-2-Bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)-3',6',18-trioxoergotaman	Generator
(5'Α)-2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)-3',6',18-trioxoergotaman	Generator
(5'a)-2-Bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)ergotaman-3',6',18-trione	Generator
(5'Α)-2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)ergotaman-3',6',18-trione	Generator
(5'a)-2-Bromo-12'-hydroxy-5'-isobutyl-2'-isopropyl-3',6',18-trioxoergotaman	Generator
(5'Α)-2-bromo-12'-hydroxy-5'-isobutyl-2'-isopropyl-3',6',18-trioxoergotaman	Generator
2-Bromo-a-ergocryptine	Generator
2-Bromo-α-ergocryptine	Generator
2-Bromo-a-ergokryptin	Generator
2-Bromo-α-ergokryptin	Generator
2-Bromo-a-ergokryptine	Generator
2-Bromo-α-ergokryptine	Generator
Bromergocryptine	HMDB
Bromocriptin	HMDB
Bromocriptine methanesulfonate	HMDB
Bromoergocryptine	HMDB
2 Bromo alpha ergocryptine	HMDB
2 Bromoergocryptine mesylate	HMDB
2 Bromoergokryptine	HMDB
2-Bromoergocryptine mesylate	HMDB
Mesylate, bromocriptine	HMDB
Methanesulfonate, 2-bromoergocryptine	HMDB
Parlodel	HMDB
2 Bromoergocryptine	HMDB
2 Bromoergocryptine methanesulfonate	HMDB
2-Bromoergocryptine	HMDB
2-Bromoergocryptine methanesulfonate	HMDB
2-Bromoergokryptine	HMDB
Mesylate, 2-bromoergocryptine	HMDB
2 Bromo alpha ergokryptine	HMDB
Bromocriptine mesylate	HMDB
Bromocryptin	HMDB

Chemical Formula

C₃₂H₄₀BrN₅O₅

Average Molecular Mass

654.595 g/mol

Monoisotopic Mass

653.221 g/mol

CAS Registry Number

25614-03-3

IUPAC Name

(4R,7R)-10-bromo-N-[(1S,2S,4R,7S)-2-hydroxy-7-(2-methylpropyl)-5,8-dioxo-4-(propan-2-yl)-3-oxa-6,9-diazatricyclo[7.3.0.0^{2,6}]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide

Traditional Name

bromocriptine

SMILES

[H][C@@]12CCCN1C(=O)[C@H](CC(C)C)N1C(=O)[C@](NC(=O)[C@H]3CN(C)[C@]4([H])CC5=C(Br)NC6=CC=CC(=C56)C4=C3)(O[C@@]21O)C(C)C

InChI Identifier

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

InChI Key

OZVBMTJYIDMWIL-AYFBDAFISA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as lysergamides. These are amides of Lysergic acids.

Kingdom

Organic compounds

Super Class

Alkaloids and derivatives

Class

Ergoline and derivatives

Sub Class

Lysergic acids and derivatives

Direct Parent

Lysergamides

Alternative Parents

Substituents

Lysergic acid amide
Indoloquinoline
Benzoquinoline
N-acyl-alpha amino acid or derivatives
Pyrroloquinoline
Alpha-amino acid or derivatives
Quinoline
3-alkylindole
Indole
Indole or derivatives
Isoindole or derivatives
Aralkylamine
N-alkylpiperazine
Aryl bromide
Aryl halide
1,4-diazinane
Oxazolidinone
Piperazine
Substituted pyrrole
Benzenoid
Heteroaromatic compound
Pyrrolidine
Pyrrole
Tertiary carboxylic acid amide
Oxazolidine
Carboxamide group
Lactam
Tertiary amine
Tertiary aliphatic amine
Orthocarboxylic acid derivative
Amino acid or derivatives
Azacycle
Oxacycle
Carboxylic acid derivative
Alkanolamine
Carboximidic acid derivative
Propargyl-type 1,3-dipolar organic compound
Carboximidic acid
Organic 1,3-dipolar compound
Organoheterocyclic compound
Organic nitrogen compound
Amine
Organopnictogen compound
Organic oxide
Carbonyl group
Organic oxygen compound
Hydrocarbon derivative
Organohalogen compound
Organobromide
Organonitrogen compound
Organooxygen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

indole alkaloid (CHEBI:3181 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	215-218°C
Boiling Point	Not Available
Solubility	8.58e-02 g/L

Predicted Properties

Property	Value	Source
Water Solubility	0.086 g/L	ALOGPS
logP	3.2	ALOGPS
logP	3.89	ChemAxon
logS	-3.9	ALOGPS
pKa (Strongest Acidic)	9.68	ChemAxon
pKa (Strongest Basic)	6.71	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	6	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	118.21 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	165.51 m³·mol⁻¹	ChemAxon
Polarizability	66.44 Å³	ChemAxon
Number of Rings	7	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-014j-9321002000-4a6a862f3d310c4b1ddc	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS ("Bromocriptine,1TMS,#1" TMS) - 70eV, Positive	Not Available	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0udi-0002009000-d51e2392ddc2f88f3e4e	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0fi0-1019002000-5ec9b007ab29026f0c68	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0udi-6029000000-f3b760903bf99f727a1f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udl-0003907000-9135b64a6bbc11172f2a	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0ika-8139817000-f971791e9c2caf9b0175	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-01ba-9301000000-344064b476a208775714	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0udi-0000009000-a432702c23226daf972f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0udi-0045019000-a5eeda23fd43d5879469	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0udi-2049004000-149f9f3768b43e24b56f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udi-0000009000-e2c1692967aaeab3212f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0udi-1031319000-12704c05dc3bfba9eb19	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00vi-9143001000-068ff47eb0d7789a1ad2	Spectrum

Toxicity Profile

Route of Exposure

Oral (18). 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 Toxicity

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. 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. (3, 4, 5, 7)

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

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

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. (15, 18)

Minimum Risk Level

Not Available

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. (2, 14, 18)

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. (16, 14)

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. (14)

Concentrations

Not Available

External Links

DrugBank ID

DB01200

HMDB ID

HMDB0015331

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

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.

MSDS

Not Available

General References

1. Malgaroli A, Vallar L, Elahi FR, Pozzan T, Spada A, Meldolesi J: Dopamine inhibits cytosolic Ca2+ increases in rat lactotroph cells. Evidence of a dual mechanism of action. J Biol Chem. 1987 Oct 15;262(29):13920-7.

2. Vallar L, Meldolesi J: Mechanisms of signal transduction at the dopamine D2 receptor. Trends Pharmacol Sci. 1989 Feb;10(2):74-7.

3. Vallar L, Vicentini LM, Meldolesi J: Inhibition of inositol phosphate production is a late, Ca2+-dependent effect of D2 dopaminergic receptor activation in rat lactotroph cells. J Biol Chem. 1988 Jul 25;263(21):10127-34.

4. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S.

5. Banihashemi B, Albert PR: Dopamine-D2S receptor inhibition of calcium influx, adenylyl cyclase, and mitogen-activated protein kinase in pituitary cells: distinct Galpha and Gbetagamma requirements. Mol Endocrinol. 2002 Oct;16(10):2393-404.

6. Nishina Y, Takano K, Yasufuku-Takano J, Teramoto A, Fujita T: Mechanism of D(2) agonist-induced inhibition of GH secretion from human GH-secreting adenoma cells. Endocr J. 2005 Dec;52(6):775-9.

7. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67.

Bromocriptine (CHEM002374)

Structure for CHEM002374: Bromocriptine