Identification

Name
Bromocriptine
Accession Number
DB01200  (APRD00622)
Type
Small Molecule
Groups
Approved, Investigational
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.

Structure
Thumb
Synonyms
  • (5'alpha)-2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)-3',6',18-trioxoergotaman
  • (5'alpha)-2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)ergotaman-3',6',18-trione
  • (5'alpha)-2-bromo-12'-hydroxy-5'-isobutyl-2'-isopropyl-3',6',18-trioxoergotaman
  • 2-Bromo-alpha-ergocryptine
  • 2-Bromo-alpha-ergokryptin
  • 2-Bromo-alpha-ergokryptine
  • 2-bromo-α-ergocryptine
  • 2-bromo-α-ergokryptin
  • 2-bromo-α-ergokryptine
  • Bromocriptina
  • Bromocriptinum
  • Bromocryptine
  • Bromoergocriptine
  • Bromoergocryptine
External IDs
SANDOZ 15-754
Product Ingredients
IngredientUNIICASInChI Key
Bromocriptine mesylateFFP983J3OD22260-51-1NOJMTMIRQRDZMT-GSPXQYRGSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BromocriptineTablet2.5 mgOralAa Pharma Inc1994-12-31Not applicableCanada
BromocriptineCapsule5 mgOralPharmel Inc1998-09-03Not applicableCanada
BromocriptineCapsule5 mgOralAa Pharma Inc1997-01-08Not applicableCanada
BromocriptineTablet2.5 mgOralPharmel Inc1998-09-03Not applicableCanada
Bromocriptine MesylateCapsule5 mg/1OralSun Pharmaceutical Industries Limited2016-12-22Not applicableUs
Bromocriptine MesylateTablet2.5 mg/1OralLek Pharmaceuticals2007-05-04Not applicableUs
Bromocriptine MesylateTablet2.5 mg/1OralSun Pharmaceutical Industries Limited2016-12-22Not applicableUs
Bromocriptine-2.5 - Tab 2.5mgTablet2.5 mgOralPro Doc Limitee1996-12-312010-07-13Canada
Bromocriptine-5Capsule5 mgOralPro Doc Limitee1998-08-112010-07-13Canada
Co Bromocriptine Capsules 5mgCapsule5 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bromocriptine MesylateCapsule5 mg/1OralAvera McKennan Hospital2016-03-082018-06-15Us
Bromocriptine mesylateTablet2.5 mg/1OralKaiser Foundations Hospitals2017-02-14Not applicableUs
Bromocriptine mesylateTablet2.5 mg/1OralSandoz1998-01-13Not applicableUs
Bromocriptine MesylateTablet2.5 mg/1OralPhysicians Total Care, Inc.2006-09-08Not applicableUs54868 566720180907 15195 13a4aek
Bromocriptine mesylateTablet2.5 mg/1OralPaddock Laboratories, LLC2014-04-01Not applicableUs00574 0106 01 nlmimage10 e039701b
Bromocriptine MesylateTablet2.5 mg/1OralMylan Pharmaceuticals Inc.2013-06-05Not applicableUs0378 204220180907 15195 1xr15w4
Bromocriptine mesylateCapsule5 mg/1OralCadila Pharnmaceuticals2009-01-23Not applicableUs
Bromocriptine MesylateTablet2.5 mg/1OralKaiser Foundations Hospitals2014-10-10Not applicableUs
Bromocriptine mesylateCapsule5 mg/1OralZydus Pharmaceuticals (USA) Inc.2009-01-23Not applicableUs
Bromocriptine mesylateTablet2.5 mg/1OralCarilion Materials Management2014-04-01Not applicableUs68151 130520180913 8702 suqlo3
International/Other Brands
Apo-Bromocriptine (Apotex) / Bagren (Serono (Brazil)) / Ergoset / Parlodel Snaptabs (Novartis) / Pravidel (Meda (Germany, Sweden), Novartis (Canada, discontinued))
Categories
UNII
3A64E3G5ZO
CAS number
25614-03-3
Weight
Average: 654.595
Monoisotopic: 653.221282062
Chemical Formula
C32H40BrN5O5
InChI Key
OZVBMTJYIDMWIL-AYFBDAFISA-N
InChI
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
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[7.3.0.0²,⁶]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0²,⁷.0¹²,¹⁶]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide
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

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.

Associated Conditions
Pharmacodynamics

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-HT1A, 5-HT2A, 5-HT1B, and 5-HT2C receptors, antagonist activity on α2A-adrenergic, α2C, α2B, and dopamine D1 receptors, partial agonist activity at receptor 5-HT2B, 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-HT2A 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-HT1B and 5-HT2B receptors.

Mechanism of action

The dopamine D2 receptor is a 7-transmembrane G-protein coupled receptor associated with Gi 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.

TargetActionsOrganism
AD(2) dopamine receptor
agonist
Human
AD(3) dopamine receptor
agonist
Human
U5-hydroxytryptamine receptor 1D
agonist
Human
UAlpha-2A adrenergic receptor
agonist
Human
U5-hydroxytryptamine receptor 1A
agonist
Human
UAlpha-2C adrenergic receptor
agonist
Human
UAlpha-2B adrenergic receptor
agonist
Human
U5-hydroxytryptamine receptor 2B
agonist
Human
UD(4) dopamine receptor
antagonist
Human
U5-hydroxytryptamine receptor 2A
agonist
Human
U5-hydroxytryptamine receptor 1B
agonist
Human
U5-hydroxytryptamine receptor 2C
agonist
Human
UD(1B) dopamine receptor
agonist
Human
UD(1A) dopamine receptor
agonist
Human
UAlpha-1A adrenergic receptor
antagonist
agonist
Human
UAlpha-1B adrenergic receptor
antagonist
agonist
Human
UAlpha-1D adrenergic receptor
agonist
Human
U5-hydroxytryptamine receptor 7
antagonist
Human
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.

Volume of distribution
Not Available
Protein binding

90-96% bound to serum albumin

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

Clearance
Not Available
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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Bromocriptine can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Bromocriptine can be decreased when combined with (S)-Warfarin.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Bromocriptine is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acidThe metabolism of Bromocriptine can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Bromocriptine.
4-MethoxyamphetamineBromocriptine may increase the hypertensive and vasoconstricting activities of 4-Methoxyamphetamine.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Bromocriptine can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
5-androstenedioneThe metabolism of Bromocriptine can be decreased when combined with 5-androstenedione.
5-methoxy-N,N-dimethyltryptamineBromocriptine may increase the vasoconstricting activities of 5-methoxy-N,N-dimethyltryptamine.
6-Deoxyerythronolide BThe metabolism of Bromocriptine can be decreased when combined with 6-Deoxyerythronolide B.
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.

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.

US5066495
General References
  1. 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. [PubMed:12351703]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
  4. 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. [PubMed:2443499]
  5. 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. [PubMed:16410672]
  6. Vallar L, Meldolesi J: Mechanisms of signal transduction at the dopamine D2 receptor. Trends Pharmacol Sci. 1989 Feb;10(2):74-7. [PubMed:2655242]
  7. 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. [PubMed:2839476]
External Links
Human Metabolome Database
HMDB0015331
KEGG Drug
D03165
KEGG Compound
C06856
PubChem Compound
31101
PubChem Substance
46505504
ChemSpider
28858
BindingDB
81993
ChEBI
3181
ChEMBL
CHEMBL493
Therapeutic Targets Database
DAP001462
PharmGKB
PA448671
HET
08Y
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Bromocriptine
ATC Codes
G02CB01 — BromocriptineN04BC01 — Bromocriptine
AHFS Codes
  • 28:36.20.04 — Ergot-derivative Dopamine Receptor Agonists
PDB Entries
3ua1 / 5vcg
FDA label
Download (105 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentEndometriosis of Uterus1
1CompletedTreatmentType 2 Diabetes Mellitus1
1, 2Not Yet RecruitingTreatmentDiabetic Macular Edema (DME)1
1, 2Not Yet RecruitingTreatmentFevers / Intracerebral Hemorrhage / Stroke, Ischemic / Subarachnoid Hemorrhage / Subdural haematoma / Traumatic Brain Injury (TBI)1
2CompletedTreatmentPeripartum Cardiomyopathy1
2Not Yet RecruitingTreatmentOvarian Hyperstimulation Syndrome1
2RecruitingTreatmentBMI >30 kg/m21
2RecruitingTreatmentDiabetes, Diabetes Mellitus Type 11
2SuspendedTreatmentMental Retardation / Stereotyped Behavior1
3CompletedTreatmentIdiopathic Parkinson's Disease1
3CompletedTreatmentParkinson's Disease (PD)2
3CompletedTreatmentType 2 Diabetes Mellitus1
3Not Yet RecruitingTreatmentPeripartum Cardiomyopathy1
3TerminatedTreatmentType 2 Diabetes Mellitus1
3Unknown StatusNot AvailableInsulin Resistance / Polycystic Ovarian Syndrome1
4Active Not RecruitingTreatmentDiabetic Autonomic Neuropathy1
4Active Not RecruitingTreatmentType 2 Diabetes Mellitus1
4CompletedTreatmentParkinson's Disease (PD)2
4CompletedTreatmentType 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentGlucose tolerance impaired / Schizophrenic Disorders1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension) / Hyperaldosteronism1
Not AvailableActive Not RecruitingBasic ScienceAddictions1
Not AvailableCompletedNot AvailableBMI >30 kg/m21
Not AvailableCompletedNot AvailableInsulin Sensitivity1
Not AvailableCompletedTreatmentCirrhosis Related Parkinsonism / Hepatic/Cirrhosis Related Parkinsonism1
Not AvailableTerminatedTreatmentGraves Ophthalmopathy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Amerisource Health Services Corp.
  • Cadila Healthcare Ltd.
  • Heartland Repack Services LLC
  • Kaiser Foundation Hospital
  • Lek Pharmaceuticals Inc.
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novartis AG
  • Paddock Labs
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Poli Industria Chimica SPA
  • Resource Optimization and Innovation LLC
  • Sandoz
  • Zydus Pharmaceuticals
Dosage forms
FormRouteStrength
CapsuleOral5 mg
TabletOral2.5 mg
CapsuleOral5 mg/1
TabletOral2.5 mg/1
TabletOral0.8 mg/1
CapsuleOral5.0 mg
Capsule, gelatin coatedOral5 mg/1
Prices
Unit descriptionCostUnit
Bromocriptine mesylate powd384.03USD g
Parlodel 5 mg capsule9.25USD capsule
Parlodel 2.5 mg tablet5.64USD tablet
Bromocriptine Mesylate 5 mg capsule5.21USD capsule
Bromocriptine Mesylate 2.5 mg tablet2.28USD tablet
Bromocriptine 2.5 mg tablet2.18USD tablet
Apo-Bromocriptine 5 mg Capsule1.02USD capsule
Pms-Bromocriptine 5 mg Capsule1.02USD capsule
Apo-Bromocriptine 2.5 mg Tablet0.57USD tablet
Pms-Bromocriptine 2.5 mg Tablet0.57USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5716957No1998-02-102015-02-10Us
US5468755No1995-11-212012-11-21Us
US8613947No2013-12-242032-04-30Us
US7888310No2011-02-152023-07-25Us
US8431155No2013-04-302032-04-30Us
US8137993No2012-03-202023-07-25Us
US8137992No2012-03-202023-07-25Us
US8137994No2012-03-202023-07-25Us
US8877708No2014-11-042030-06-07Us
US9192576No2015-11-242032-04-30Us
US9522117No2016-12-202032-04-30Us
US9352025No2016-05-312030-06-07Us
US9700555No2017-07-112032-04-30Us
US9895422No2018-02-202030-06-07Us
US9993474No2012-04-302032-04-30Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)215-218Fluckiger, E.,Troxler, F. and Hofmann, A,; US. Patent 3,752,814; August 14, 1973; assigned to Sandoz Ltd., Switzerland. Fluckiger, E., Troxler, F. and Hofmann, A.; U.S. Patent 3,752,888; August 14, 1973; assigned to Sandoz Ltd., Switzerland.
logP3.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0858 mg/mLALOGPS
logP3.2ALOGPS
logP3.89ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)9.68ChemAxon
pKa (Strongest Basic)6.71ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area118.21 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity165.51 m3·mol-1ChemAxon
Polarizability66.44 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.915
Blood Brain Barrier-0.9845
Caco-2 permeable-0.6618
P-glycoprotein substrateSubstrate0.8881
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.8388
Renal organic cation transporterNon-inhibitor0.837
CYP450 2C9 substrateNon-substrate0.8345
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7454
CYP450 1A2 substrateNon-inhibitor0.9031
CYP450 2C9 inhibitorInhibitor0.8326
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5149
Ames testNon AMES toxic0.7879
CarcinogenicityNon-carcinogens0.9353
BiodegradationNot ready biodegradable0.9973
Rat acute toxicity2.7499 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9313
hERG inhibition (predictor II)Inhibitor0.5
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound 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
Indoloquinolines / Benzoquinolines / Pyrroloquinolines / N-acyl-alpha amino acids and derivatives / 3-alkylindoles / Isoindoles and derivatives / Aralkylamines / N-alkylpiperazines / Aryl bromides / Benzenoids
show 18 more
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
show 42 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
indole alkaloid (CHEBI:3181)

Targets

Details
1. D(2) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Cavallotti C, Nuti F, Bruzzone P, Mancone M: Age-related changes in dopamine D2 receptors in rat heart and coronary vessels. Clin Exp Pharmacol Physiol. 2002 May-Jun;29(5-6):412-8. [PubMed:12010185]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  3. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  4. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
  5. Lahlou S: Cardiovascular responses to intrathecal dopamine receptor agonists in conscious DOCA-salt hypertensive rats. Fundam Clin Pharmacol. 1999;13(6):624-34. [PubMed:10626749]
  6. Lahlou S, Araujo Lima PF, Interaminense LF, Duarte GP: Blunted central bromocriptine-induced tachycardia in conscious, malnourished rats. Pharmacol Toxicol. 2003 Apr;92(4):189-94. [PubMed:12753422]
  7. Lahlou S, Lima GC, Leao-Filho CS, Duarte GP: Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats. Can J Physiol Pharmacol. 2000 Mar;78(3):260-5. [PubMed:10721819]
  8. Stefaneanu L, Kovacs K, Horvath E, Buchfelder M, Fahlbusch R, Lancranjan L: Dopamine D2 receptor gene expression in human adenohypophysial adenomas. Endocrine. 2001 Apr;14(3):329-36. [PubMed:11444429]
Details
2. D(3) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name
DRD3
Uniprot ID
P35462
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44224.335 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1D
Uniprot ID
P28221
Uniprot Name
5-hydroxytryptamine receptor 1D
Molecular Weight
41906.38 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. de Leeuw van Weenen JE, Parlevliet ET, Maechler P, Havekes LM, Romijn JA, Ouwens DM, Pijl H, Guigas B: The dopamine receptor D2 agonist bromocriptine inhibits glucose-stimulated insulin secretion by direct activation of the alpha2-adrenergic receptors in beta cells. Biochem Pharmacol. 2010 Jun 15;79(12):1827-36. doi: 10.1016/j.bcp.2010.01.029. Epub 2010 Feb 4. [PubMed:20138024]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
References
  1. de Leeuw van Weenen JE, Parlevliet ET, Maechler P, Havekes LM, Romijn JA, Ouwens DM, Pijl H, Guigas B: The dopamine receptor D2 agonist bromocriptine inhibits glucose-stimulated insulin secretion by direct activation of the alpha2-adrenergic receptors in beta cells. Biochem Pharmacol. 2010 Jun 15;79(12):1827-36. doi: 10.1016/j.bcp.2010.01.029. Epub 2010 Feb 4. [PubMed:20138024]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Epinephrine binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
References
  1. de Leeuw van Weenen JE, Parlevliet ET, Maechler P, Havekes LM, Romijn JA, Ouwens DM, Pijl H, Guigas B: The dopamine receptor D2 agonist bromocriptine inhibits glucose-stimulated insulin secretion by direct activation of the alpha2-adrenergic receptors in beta cells. Biochem Pharmacol. 2010 Jun 15;79(12):1827-36. doi: 10.1016/j.bcp.2010.01.029. Epub 2010 Feb 4. [PubMed:20138024]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I: Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. Eur J Pharmacol. 2008 Oct 10;594(1-3):32-8. doi: 10.1016/j.ejphar.2008.07.040. Epub 2008 Jul 30. [PubMed:18703043]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Sh3 domain binding
Specific Function
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins ...
Gene Name
DRD4
Uniprot ID
P21917
Uniprot Name
D(4) dopamine receptor
Molecular Weight
48359.86 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I: Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. Eur J Pharmacol. 2008 Oct 10;594(1-3):32-8. doi: 10.1016/j.ejphar.2008.07.040. Epub 2008 Jul 30. [PubMed:18703043]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1B
Uniprot ID
P28222
Uniprot Name
5-hydroxytryptamine receptor 1B
Molecular Weight
43567.535 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I: Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells. Eur J Pharmacol. 2008 Oct 10;594(1-3):32-8. doi: 10.1016/j.ejphar.2008.07.040. Epub 2008 Jul 30. [PubMed:18703043]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Details
13. D(1B) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD5
Uniprot ID
P21918
Uniprot Name
D(1B) dopamine receptor
Molecular Weight
52950.5 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
Details
14. D(1A) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
Agonist
Curator comments
Bromocriptine displays low affinity towards alpha-1 adrenoceptor. In vitro, bromocriptine acts as an antagonist in postsynaptic alpha-1 adrenoceptors expressed in smooth muscle cells.
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
  2. Gibson A, Samini M: The effects of bromocriptine on pre-synaptic and post-synaptic alpha-adrenoceptors in the mouse vas deferens. J Pharm Pharmacol. 1979 Dec;31(12):826-30. [PubMed:43367]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
Agonist
Curator comments
Bromocriptine displays low affinity towards alpha-1 adrenoceptor. In vitro, bromocriptine acts as an antagonist in postsynaptic alpha-1 adrenoceptors expressed in smooth muscle cells.
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
  2. Gibson A, Samini M: The effects of bromocriptine on pre-synaptic and post-synaptic alpha-adrenoceptors in the mouse vas deferens. J Pharm Pharmacol. 1979 Dec;31(12):826-30. [PubMed:43367]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [PubMed:10641988]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. Knight JA, Smith C, Toohey N, Klein MT, Teitler M: Pharmacological analysis of the novel, rapid, and potent inactivation of the human 5-Hydroxytryptamine7 receptor by risperidone, 9-OH-Risperidone, and other inactivating antagonists. Mol Pharmacol. 2009 Feb;75(2):374-80. doi: 10.1124/mol.108.052084. Epub 2008 Nov 7. [PubMed:18996971]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Fernando H, Halpert JR, Davydov DR: Resolution of multiple substrate binding sites in cytochrome P450 3A4: the stoichiometry of the enzyme-substrate complexes probed by FRET and Job's titration. Biochemistry. 2006 Apr 4;45(13):4199-209. [PubMed:16566594]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132]
  3. Nath A, Grinkova YV, Sligar SG, Atkins WM: Ligand binding to cytochrome P450 3A4 in phospholipid bilayer nanodiscs: the effect of model membranes. J Biol Chem. 2007 Sep 28;282(39):28309-20. Epub 2007 Jun 15. [PubMed:17573349]
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol. 2002 May;61(5):964-73. [PubMed:11961113]
  2. Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. [PubMed:12235267]
  3. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. [PubMed:12438524]
  4. Renaud JP, Davydov DR, Heirwegh KP, Mansuy D, Hui Bon Hoa GH: Thermodynamic studies of substrate binding and spin transitions in human cytochrome P-450 3A4 expressed in yeast microsomes. Biochem J. 1996 Nov 1;319 ( Pt 3):675-81. [PubMed:8920966]

Drug created on June 13, 2005 07:24 / Updated on November 20, 2018 00:52