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Identification
Name Bromocriptine
Accession Number DB01200 (APRD00622)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Bromergocryptine
Bromocriptin
Bromocriptina [INN-Spanish]
Bromocriptine Mesylate
Bromocriptine Methanesulfonate
Bromocriptinum [INN-Latin]
Bromocryptine
Bromocryptine Mesylate
Bromoergocriptine
Bromoergocryptine
Salts Not Available
Brand names
Name Company
Alti-Bromocriptine
Apo-Bromocriptine Apotex
Bagren Serono (Brazil)
Ergoset
Parlodel Novartis
Parlodel Snaptabs Novartis
Pravidel Meda (Germany, Sweden), Novartis (Canada, discontinued)
Brand mixtures Not Available
Categories
  • Antiparkinson Agents
  • Antidyskinetics
  • Dopamine Agonists
  • Hormone Antagonists
CAS number 25614-03-3
Weight Average: 654.595
Monoisotopic: 653.221282062
Chemical Formula C32H40BrN5O5
InChI Key InChIKey=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
Plain Text
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
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Ergolines
  • Lactams
  • Indoloquinolines
Substructures
  • Ergolines
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Indoles and Indole Derivatives
  • Carboxylic Acids and Derivatives
  • Amino Ketones
  • Phenylpropenes
  • Pyrroles
  • Piperazines
  • Pyrrolidines
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Aryl Halides
  • Isoprenes
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Tryptamines and Derivatives
  • Lactams
  • Pyrrolopyrazines
  • Amphetamines
  • Indoloquinolines
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.
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.
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
Pharmacoeconomics
Manufacturers
  • Lek pharmaceutical and chemical co dd
  • Mylan pharmaceuticals inc
  • Zydus pharmaceuticals usa inc
  • Novartis pharmaceuticals corp
  • Lek pharmaceuticals d d
  • Paddock laboratories inc
  • Veroscience llc
Packagers
Dosage forms
Form Route Strength
Capsule Oral 5 mg
Tablet Oral 2.5 mg
Prices
Unit description Cost Unit
Bromocriptine mesylate powd 384.03 USD g
Parlodel 5 mg capsule 9.25 USD capsule
Parlodel 2.5 mg tablet 5.64 USD tablet
Bromocriptine Mesylate 5 mg capsule 5.21 USD capsule
Bromocriptine Mesylate 2.5 mg tablet 2.28 USD tablet
Bromocriptine 2.5 mg tablet 2.18 USD tablet
Apo-Bromocriptine 5 mg Capsule 1.02 USD capsule
Pms-Bromocriptine 5 mg Capsule 1.02 USD capsule
Apo-Bromocriptine 2.5 mg Tablet 0.57 USD tablet
Pms-Bromocriptine 2.5 mg Tablet 0.57 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 5716957 1995-02-10 2015-02-10
United States 5468755 1992-11-21 2012-11-21
Properties
State solid
Experimental Properties
Property Value Source
logP 3.5 Not Available
Predicted Properties
Property Value Source
water solubility 8.58e-02 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 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 165.51 ChemAxon
polarizability 66.44 ChemAxon
References
Synthesis Reference Not Available
General Reference
  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
  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
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed
  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
  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
  6. Vallar L, Meldolesi J: Mechanisms of signal transduction at the dopamine D2 receptor. Trends Pharmacol Sci. 1989 Feb;10(2):74-7. Pubmed
  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
External Links
Resource Link
KEGG Drug D03165 Link_out
KEGG Compound C06856 Link_out
PubChem Compound 31101 Link_out
PubChem Substance 46505504 Link_out
ChemSpider 28858 Link_out
ChEBI 3181 Link_out
ChEMBL 3181 Link_out
Therapeutic Targets Database DAP001462 Link_out
PharmGKB PA448671 Link_out
Drug Product Database 2236949 Link_out
RxList http://www.rxlist.com/cgi/generic3/bromocriptine.htm Link_out
Drugs.com http://www.drugs.com/cdi/bromocriptine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Bromocriptine Link_out
ATC Codes
  • G02CB01
  • N04BC01
AHFS Codes
  • 28:36.20.04
PDB Entries Not Available
FDA label show (105 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Acetophenazine The phenothiazine decreases the effect of bromocriptine
Chlorpromazine The phenothiazine decreases the effect of bromocriptine
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Erythromycin Erythromycin increases serum levels of bromocriptine
Ethopropazine The phenothiazine decreases the effect of bromocriptine
Fluphenazine The phenothiazine decreases the effect of bromocriptine
Josamycin Erythromycin increases serum levels of bromocriptine
Mesoridazine The phenothiazine decreases the effect of bromocriptine
Methdilazine The phenothiazine decreases the effect of bromocriptine
Methotrimeprazine 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.
Perphenazine The phenothiazine decreases the effect of bromocriptine
Phenylpropanolamine The sympathomimetic, phenylpropanolamine, increases the toxicity of bromocriptine.
Prochlorperazine The phenothiazine decreases the effect of bromocriptine
Promazine The phenothiazine decreases the effect of bromocriptine
Promethazine The phenothiazine decreases the effect of bromocriptine
Propiomazine The phenothiazine decreases the effect of bromocriptine
Pseudoephedrine The sympathomimetic, pseudoephedrine, increases the toxicity 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.
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.
Thiethylperazine The phenothiazine decreases the effect of bromocriptine
Thioridazine 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.
Tipranavir Tipranavir may increase the plasma concentration of Bromocriptine. Concomitant therapy should be avoided.
Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trifluoperazine The phenothiazine decreases the effect of bromocriptine
Triflupromazine The phenothiazine decreases the effect of bromocriptine
Trimeprazine The phenothiazine decreases the effect of bromocriptine
Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Voriconazole Voriconazole may increase the serum concentration of bromocriptine likely by decreasing its metabolism. Concomitant therapy is contraindicated.
Ziprasidone The atypical antipsychotic, ziprasidone, may antagonize the effect of the dopamine agonist, bromocriptine. Consider alternate therapy or monitor for worsening of movement disorder.
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.
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.
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.
Targets

1. D(2) dopamine receptor

Pharmacological action: yes
Actions: agonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out
Gene: DRD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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
  4. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed
  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
  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
  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
  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

2. D(3) dopamine receptor

Pharmacological action: yes
Actions: agonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P35462 Link_out
Gene: DRD3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

3. 5-hydroxytryptamine 1D receptor

Pharmacological action: unknown
Actions: agonist

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 is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28221 Link_out
Gene: HTR1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

4. Alpha-2A adrenergic receptor

Pharmacological action: unknown
Actions: agonist

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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Organism class: human
UniProt ID: P08913 Link_out
Gene: ADRA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2010 Feb 4. Pubmed
  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
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

5. 5-hydroxytryptamine 1A receptor

Pharmacological action: unknown
Actions: agonist

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 is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P08908 Link_out
Gene: HTR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

6. Alpha-2C adrenergic receptor

Pharmacological action: unknown
Actions: agonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins

Organism class: human
UniProt ID: P18825 Link_out
Gene: ADRA2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2010 Feb 4. Pubmed
  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
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

7. Alpha-2B adrenergic receptor

Pharmacological action: unknown
Actions: agonist

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 > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol

Organism class: human
UniProt ID: P18089 Link_out
Gene: ADRA2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2010 Feb 4. Pubmed
  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
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

8. 5-hydroxytryptamine 2B receptor

Pharmacological action: unknown
Actions: agonist

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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P41595 Link_out
Gene: HTR2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2008 Jul 30. Pubmed
  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
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

9. D(4) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P21917 Link_out
Gene: DRD4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

10. 5-hydroxytryptamine 2A receptor

Pharmacological action: unknown
Actions: agonist

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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2008 Jul 30. Pubmed
  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
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

11. 5-hydroxytryptamine 1B receptor

Pharmacological action: unknown
Actions: agonist

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 is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28222 Link_out
Gene: HTR1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

12. 5-hydroxytryptamine 2C receptor

Pharmacological action: unknown
Actions: agonist

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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P28335 Link_out
Gene: HTR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2008 Jul 30. Pubmed
  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
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

13. D(1B) dopamine receptor

Pharmacological action: unknown
Actions: agonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21918 Link_out
Gene: DRD5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

14. D(1A) dopamine receptor

Pharmacological action: unknown
Actions: agonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21728 Link_out
Gene: DRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

15. Alpha-1A adrenergic receptor

Pharmacological action: unknown
Actions: agonist

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) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

16. Alpha-1B adrenergic receptor

Pharmacological action: unknown
Actions: agonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P35368 Link_out
Gene: ADRA1B Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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

17. Alpha-1D adrenergic receptor

Pharmacological action: unknown
Actions: agonist

This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium

Organism class: human
UniProt ID: P25100 Link_out
Gene: ADRA1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

18. 5-hydroxytryptamine 7 receptor

Pharmacological action: unknown
Actions: antagonist

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 is mediated by G proteins that stimulate adenylate cyclase

Organism class: human
UniProt ID: P34969 Link_out
Gene: HTR7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2008 Nov 7. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: substrate, inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19