Bromocriptine (T3D3017)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (25)XML
Targets (25)
Record Information
Version2.0
Creation Date2009-07-21 20:28:37 UTC
Update Date2014-12-24 20:25:55 UTC
Accession NumberT3D3017
Identification
Common NameBromocriptine
ClassSmall Molecule
DescriptionBromocriptine 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.
Compound Type
  • Amide
  • Amine
  • Antidyskinetic
  • Antiparkinson Agent
  • Bromide Compound
  • Dopamine Agonist
  • Drug
  • Ether
  • Hormone Antagonist
  • Metabolite
  • Organic Compound
  • Organobromide
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(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
Apo-Bromocriptine
Bagren
Bromergocryptine
Bromocriptin
Bromocriptina
Bromocriptine Methanesulfonate
Bromocriptinum
Bromocryptine
Bromoergocriptine
Bromoergocryptine
CYCLOSET
Ergoset
Parlodel
Parlodel Snaptabs
Pravidel
Chemical FormulaC32H40BrN5O5
Average Molecular Mass654.595 g/mol
Monoisotopic Mass653.221 g/mol
CAS Registry Number25614-03-3
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[7.3.0.0²,⁶]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
Traditional Namebromocriptine
SMILES[H][C@@]12CCCN1C(=O)[C@]([H])(CC(C)C)N1C(=O)[C@@](O[C@@]21O)(N=C(O)[C@@]1([H])CN(C)[C@]2([H])CC3=C(Br)NC4=CC=CC(=C34)C2=C1)C(C)C
InChI IdentifierInChI=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 KeyInChIKey=OZVBMTJYIDMWIL-AYFBDAFISA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as lysergamides. These are amides of Lysergic acids.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassErgoline and derivatives
Sub ClassLysergic acids and derivatives
Direct ParentLysergamides
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 FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point215-218°C
Boiling PointNot Available
Solubility8.58e-02 g/L
LogP3.5
Predicted Properties
PropertyValueSource
Water Solubility0.086 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity165.51 m³·mol⁻¹ChemAxon
Polarizability66.44 ųChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-014j-9321002000-4a6a862f3d310c4b1ddc2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-10-17View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-10-17View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot Available2021-10-17View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-10-17View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-10-17View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, PositiveNot Available2021-10-17View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS ("Bromocriptine,1TMS,#1" TMS) - 70eV, PositiveNot Available2021-11-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0002009000-d51e2392ddc2f88f3e4e2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fi0-1019002000-5ec9b007ab29026f0c682016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-6029000000-f3b760903bf99f727a1f2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udl-0003907000-9135b64a6bbc11172f2a2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0ika-8139817000-f971791e9c2caf9b01752016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01ba-9301000000-344064b476a2087757142016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0000009000-a432702c23226daf972f2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0045019000-a5eeda23fd43d58794692021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-2049004000-149f9f3768b43e24b56f2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0000009000-e2c1692967aaeab3212f2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-1031319000-12704c05dc3bfba9eb192021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00vi-9143001000-068ff47eb0d7789a1ad22021-10-11View Spectrum
Toxicity Profile
Route of ExposureOral (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 ToxicityThe 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. 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. (2, 3, 4, 5)
MetabolismCompletely 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 ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor 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 LevelNot Available
Health EffectsA 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. (1, 14, 18)
SymptomsSide 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)
TreatmentTreatment 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)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01200
HMDB IDHMDB15331
PubChem Compound ID31101
ChEMBL IDCHEMBL493
ChemSpider ID28858
KEGG IDC06856
UniProt IDNot Available
OMIM ID
ChEBI ID3181
BioCyc IDNot Available
CTD IDNot Available
Stitch IDBromocriptine
PDB ID08Y
ACToR IDNot Available
Wikipedia LinkBromocriptine
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.

MSDST3D3017.pdf
General References
  1. Richard JL: Some major mycotoxins and their mycotoxicoses--an overview. Int J Food Microbiol. 2007 Oct 20;119(1-2):3-10. Epub 2007 Jul 31. [17719115 ]
  2. Mantegani S, Brambilla E, Varasi M: Ergoline derivatives: receptor affinity and selectivity. Farmaco. 1999 May 30;54(5):288-96. [10418123 ]
  3. Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
  4. Kvernmo T, Hartter S, Burger E: A review of the receptor-binding and pharmacokinetic properties of dopamine agonists. Clin Ther. 2006 Aug;28(8):1065-78. [16982285 ]
  5. Coldwell MC, Boyfield I, Brown T, Hagan JJ, Middlemiss DN: Comparison of the functional potencies of ropinirole and other dopamine receptor agonists at human D2(long), D3 and D4.4 receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1999 Aug;127(7):1696-702. [10455328 ]
  6. 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. [12351703 ]
  7. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [18691132 ]
  8. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  9. 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. [2443499 ]
  10. 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. [16410672 ]
  11. Vallar L, Meldolesi J: Mechanisms of signal transduction at the dopamine D2 receptor. Trends Pharmacol Sci. 1989 Feb;10(2):74-7. [2655242 ]
  12. 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. [2839476 ]
  13. Drugs.com [Link]
  14. RxList: The Internet Drug Index (2009). [Link]
  15. Wikipedia. Ergoline. Last Updated 2 April 2010. [Link]
  16. Wikipedia. Ergotism. Last Updated 6 April 2010. [Link]
  17. Van den Enden, E. (2004). Illustrated Lecture Notes on Tropical Medicine. [Link]
  18. Wikipedia. Bromocriptine. Last Updated 20 April 2010. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

Target Details
1. D(2) dopamine receptor
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
Molecular Weight:
50618.91 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.01 uMNot AvailableBindingDB 50026707
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Lahlou S: Cardiovascular responses to intrathecal dopamine receptor agonists in conscious DOCA-salt hypertensive rats. Fundam Clin Pharmacol. 1999;13(6):624-34. [10626749 ]
  3. 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. [10721819 ]
  4. 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. [11444429 ]
  5. 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. [12010185 ]
  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. [12753422 ]
  7. Coldwell MC, Boyfield I, Brown T, Hagan JJ, Middlemiss DN: Comparison of the functional potencies of ropinirole and other dopamine receptor agonists at human D2(long), D3 and D4.4 receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1999 Aug;127(7):1696-702. [10455328 ]
  8. Heier RF, Dolak LA, Duncan JN, Hyslop DK, Lipton MF, Martin IJ, Mauragis MA, Piercey MF, Nichols NF, Schreur PJ, Smith MW, Moon MW: Synthesis and biological activities of (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and its metabolites. J Med Chem. 1997 Feb 28;40(5):639-46. [9057850 ]
Target Details
2. 5-hydroxytryptamine receptor 1A
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 signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular Weight:
46106.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.01288 uMNot AvailableBindingDB 50026707
Inhibitory0.024 uMNot AvailableBindingDB 50026707
Inhibitory0.025 uMNot AvailableBindingDB 50026707
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. [18691132 ]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  3. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
  4. Heier RF, Dolak LA, Duncan JN, Hyslop DK, Lipton MF, Martin IJ, Mauragis MA, Piercey MF, Nichols NF, Schreur PJ, Smith MW, Moon MW: Synthesis and biological activities of (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and its metabolites. J Med Chem. 1997 Feb 28;40(5):639-46. [9057850 ]
  5. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
Target Details
3. Adenylate cyclase type 7
General Function:
Metal ion binding
Specific Function:
This is a membrane-bound, calcium-inhibitable adenylyl cyclase.
Gene Name:
ADCY7
Uniprot ID:
P51828
Molecular Weight:
120307.175 Da
References
  1. Chen JC, Su HJ, Huang LI, Hsieh MM: Reductions in binding and functions of D2 dopamine receptors in the rat ventral striatum during amphetamine sensitization. Life Sci. 1999;64(5):343-54. [10072194 ]
  2. Coronas V, Krantic S, Jourdan F, Moyse E: Dopamine receptor coupling to adenylyl cyclase in rat olfactory pathway: a combined pharmacological-radioautographic approach. Neuroscience. 1999 Apr;90(1):69-78. [10188934 ]
  3. Izquierdo-Claros RM, del Boyano-Adanez M, Arilla-Ferreiro E: Activation of D1 and D2 dopamine receptors increases the activity of the somatostatin receptor-effector system in the rat frontoparietal cortex. J Neurosci Res. 2000 Oct 1;62(1):91-8. [11002291 ]
  4. Kan SF, Kau MM, Low-Tone Ho L, Wang PS: Inhibitory effects of bromocriptine on corticosterone secretion in male rats. Eur J Pharmacol. 2003 May 9;468(2):141-9. [12742521 ]
  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. [16410672 ]
Target Details
4. 5-hydroxytryptamine receptor 2A
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-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular Weight:
52602.58 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.10715 uMNot AvailableBindingDB 50026707
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. [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. [18691132 ]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  4. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
5. 5-hydroxytryptamine receptor 2C
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-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular Weight:
51820.705 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.74131 uMNot AvailableBindingDB 50026707
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. [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. [18691132 ]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  4. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
6. Alpha-2A adrenergic receptor
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 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.
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.01096 uMNot AvailableBindingDB 50026707
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. [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. [18691132 ]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  4. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
7. Alpha-2B adrenergic receptor
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 > 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.
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.03467 uMNot AvailableBindingDB 50026707
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. [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. [18691132 ]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  4. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
8. Alpha-2C adrenergic receptor
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
Molecular Weight:
49521.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.02818 uMNot AvailableBindingDB 50026707
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. [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. [18691132 ]
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  4. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
9. D(1A) dopamine receptor
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
Molecular Weight:
49292.765 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.672 uMNot AvailableBindingDB 50026707
Inhibitory0.69183 uMNot AvailableBindingDB 50026707
Inhibitory2.07 uMNot AvailableBindingDB 50026707
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. [18691132 ]
  2. Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB: Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature. 1991 Apr 18;350(6319):614-9. [1826762 ]
  3. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
  4. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
Target Details
10. 5-hydroxytryptamine receptor 1D
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 substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.
Gene Name:
HTR1D
Uniprot ID:
P28221
Molecular Weight:
41906.38 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.01072 uMNot AvailableBindingDB 50026707
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. [18691132 ]
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  3. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
11. Cyclic AMP-responsive element-binding protein 1
General Function:
Transcriptional activator activity, rna polymerase ii transcription factor binding
Specific Function:
Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.
Gene Name:
CREB1
Uniprot ID:
P16220
Molecular Weight:
36687.86 Da
References
  1. Kashihara K, Ishihara T, Akiyama K, Abe K: D1/D2 receptor synergism on CREB DNA-binding activities in the caudate-putamen of rat. Neurol Res. 1999 Dec;21(8):781-4. [10596389 ]
  2. Ozawa A, Yamada M, Satoh T, Monden T, Hashimoto K, Kohga H, Hashiba Y, Sasaki T, Mori M: Transcriptional regulation of the human PRL-releasing peptide (PrRP) receptor gene by a dopamine 2 Receptor agonist: cloning and characterization of the human PrRP receptor gene and its promoter region. Mol Endocrinol. 2002 Apr;16(4):785-98. [11923475 ]
  3. Kashihara K, Ishihara T, Akiyama K, Kuroda S, Morimasa T, Shomori T: Levodopa induces AP-1 and CREB DNA-binding activities in the rat striatum. Psychiatry Clin Neurosci. 1995 Dec;49(5-6):291-4. [8726116 ]
Target Details
12. Cytochrome P450 3A4
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 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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
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. [16566594 ]
  2. 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. [17573349 ]
  3. Rasmussen BB, Nielsen TL, Brosen K: Fluvoxamine is a potent inhibitor of the metabolism of caffeine in vitro. Pharmacol Toxicol. 1998 Dec;83(6):240-5. [9868741 ]
Target Details
13. D(1B) dopamine receptor
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
Molecular Weight:
52950.5 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.454 uMNot AvailableBindingDB 50026707
Inhibitory0.53703 uMNot AvailableBindingDB 50026707
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. [18691132 ]
  2. Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB: Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature. 1991 Apr 18;350(6319):614-9. [1826762 ]
  3. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
14. Somatostatin
General Function:
Hormone activity
Specific Function:
Somatostatin inhibits the release of somatotropin.
Gene Name:
SST
Uniprot ID:
P61278
Molecular Weight:
12735.395 Da
References
  1. Soule SG, Macfarlane P, Levitt NS, Millar RP: Contribution of growth hormone-releasing hormone and somatostatin to decreased growth hormone secretion in elderly men. S Afr Med J. 2001 Mar;91(3):254-60. [11291426 ]
  2. Todisco M, Casaccia P, Rossi N: Cyclophosphamide plus somatostatin, bromocriptin, retinoids, melatonin and ACTH in the treatment of low-grade non-Hodgkin's lymphomas at advanced stage: results of a phase II trial. Cancer Biother Radiopharm. 2001 Apr;16(2):171-7. [11385964 ]
  3. Gasparoni P, Rubello D, Persani L, Beck-Peccoz P: Unusual association between a thyrotropin-secreting pituitary adenoma and a papillary thyroid carcinoma. Thyroid. 1998 Feb;8(2):181-3. [9510128 ]
Target Details
15. 5-hydroxytryptamine receptor 1B
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 substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
Gene Name:
HTR1B
Uniprot ID:
P28222
Molecular Weight:
43567.535 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.35481 uMNot AvailableBindingDB 50026707
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. [18691132 ]
  2. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
16. 5-hydroxytryptamine receptor 2B
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 change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine.
Gene Name:
HTR2B
Uniprot ID:
P41595
Molecular Weight:
54297.41 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.05623 uMNot AvailableBindingDB 50026707
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. [18691132 ]
  2. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
17. 5-hydroxytryptamine receptor 7
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 is mediated by G proteins that stimulate adenylate cyclase.
Gene Name:
HTR7
Uniprot ID:
P34969
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. [18996971 ]
  2. Toohey N, Klein MT, Knight J, Smith C, Teitler M: Human 5-HT7 receptor-induced inactivation of forskolin-stimulated adenylate cyclase by risperidone, 9-OH-risperidone and other "inactivating antagonists". Mol Pharmacol. 2009 Sep;76(3):552-9. doi: 10.1124/mol.109.056283. Epub 2009 Jun 9. [19509219 ]
Target Details
18. Alpha-1B adrenergic receptor
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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.00138 uMNot AvailableBindingDB 50026707
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  2. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
19. Alpha-1D adrenergic receptor
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
Molecular Weight:
60462.205 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.00112 uMNot AvailableBindingDB 50026707
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
  2. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
20. Cytochrome P450 3A4
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 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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC503 uMNot AvailableBindingDB 50026707
References
  1. Roy K, Pratim Roy P: Comparative chemometric modeling of cytochrome 3A4 inhibitory activity of structurally diverse compounds using stepwise MLR, FA-MLR, PLS, GFA, G/PLS and ANN techniques. Eur J Med Chem. 2009 Jul;44(7):2913-22. doi: 10.1016/j.ejmech.2008.12.004. Epub 2008 Dec 16. [19128860 ]
  2. Tsalkova TN, Davydova NY, Halpert JR, Davydov DR: Mechanism of interactions of alpha-naphthoflavone with cytochrome P450 3A4 explored with an engineered enzyme bearing a fluorescent probe. Biochemistry. 2007 Jan 9;46(1):106-19. [17198380 ]
Target Details
21. D(3) dopamine receptor
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
Molecular Weight:
44224.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.087 uMNot AvailableBindingDB 50026707
References
  1. Coldwell MC, Boyfield I, Brown T, Hagan JJ, Middlemiss DN: Comparison of the functional potencies of ropinirole and other dopamine receptor agonists at human D2(long), D3 and D4.4 receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1999 Aug;127(7):1696-702. [10455328 ]
  2. Heier RF, Dolak LA, Duncan JN, Hyslop DK, Lipton MF, Martin IJ, Mauragis MA, Piercey MF, Nichols NF, Schreur PJ, Smith MW, Moon MW: Synthesis and biological activities of (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and its metabolites. J Med Chem. 1997 Feb 28;40(5):639-46. [9057850 ]
Target Details
22. 5-hydroxytryptamine receptor 6
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 is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
Gene Name:
HTR6
Uniprot ID:
P50406
Molecular Weight:
46953.625 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.033 uMNot AvailableBindingDB 50026707
References
  1. Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW: Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor. J Neurochem. 1996 Jan;66(1):47-56. [8522988 ]
Target Details
23. Alpha-1A adrenergic receptor
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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
References
  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. [10641988 ]
Target Details
24. Beta-1 adrenergic receptor
General Function:
Receptor signaling protein activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular Weight:
51322.1 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.58884 uMNot AvailableBindingDB 50026707
References
  1. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804. [12388666 ]
Target Details
25. D(4) dopamine receptor
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 which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).
Gene Name:
DRD4
Uniprot ID:
P21917
Molecular Weight:
48359.86 Da
References
  1. Coldwell MC, Boyfield I, Brown T, Hagan JJ, Middlemiss DN: Comparison of the functional potencies of ropinirole and other dopamine receptor agonists at human D2(long), D3 and D4.4 receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1999 Aug;127(7):1696-702. [10455328 ]