T3DB: Dopamine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (15)XML

Targets (15)

Record Information

Version

2.0

Creation Date

2014-08-29 06:17:08 UTC

Update Date

2018-03-21 17:46:16 UTC

Accession Number

T3D4300

Identification

Common Name

Dopamine

Class

Small Molecule

Description

Dopamine is a member of the catecholamine family of neurotransmitters in the brain and is a precursor to epinephrine (adrenaline) and norepinephrine (noradrenaline). Dopamine is synthesized in the body (mainly by nervous tissue and adrenal glands) first by the hydration of the amino acid tyrosine to DOPA by tyrosine hydroxylase and then by the decarboxylation of DOPA by aromatic-L-amino-acid decarboxylase. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (dopamine receptors) mediates its action, which plays a major role in reward-motivated behaviour. Dopamine has many other functions outside the brain. In blood vessels, dopamine inhibits norepinephrine release and acts as a vasodilator (at normal concentrations); in the kidneys, it increases sodium excretion and urine output; in the pancreas, it reduces insulin production; in the digestive system, it reduces gastrointestinal motility and protects intestinal mucosa; and in the immune system, it reduces the activity of lymphocytes. Parkinson's disease, a degenerative condition causing tremor and motor impairment, is caused by a loss of dopamine-secreting neurons in an area of the midbrain called the substantia nigra. There is evidence that schizophrenia involves altered levels of dopamine activity, and most antipsychotic drugs used to treat this are dopamine antagonists, which reduce dopamine activity. Attention deficit hyperactivity disorder, bipolar disorder, and addiction are also characterized by defects in dopamine production or metabolism. It has been suggested that animals derived their dopamine-synthesizing machinery from bacteria via horizontal gene transfer that may have occurred relatively late in evolutionary time. This is perhaps a result of the symbiotic incorporation of bacteria into eukaryotic cells that gave rise to mitochondria. Dopamine is elevated in the urine of people who consume bananas. When present in sufficiently high levels, dopamine can be a neurotoxin and a metabotoxin. A neurotoxin is a compound that disrupts or attacks neural tissue. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of dopamine are associated with neuroblastoma, Costello syndrome, leukemia, phaeochromocytoma, aromatic L-amino acid decarboxylase deficiency, and Menkes disease (MNK). High levels of dopamine can lead to hyperactivity, insomnia, agitation and anxiety, depression, delusions, excessive salivation, nausea, and digestive problems.

Compound Type

Amine
Animal Toxin
Cardiotonic Agent
Dopamine Agent
Drug
Food Toxin
Metabolite
Natural Compound
Organic Compound
Sympathomimetic

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
2-(3,4-Dihydroxyphenyl)ethylamine
3,4-Dihydroxyphenethylamine
3,4-Dihydroxyphenylethylamine
3-Hydroxytyramine
4-(2-Aminoethyl)-1,2-benzenediol
4-(2-Aminoethyl)-Pyrocatechol
4-(2-Aminoethyl)benzene-1,2-diol
4-(2-Aminoethyl)catechol
4-(2-Aminoethyl)pyrocatechol
a-(3,4-Dihydroxyphenyl)-b-aminoethane
alpha-(3,4-Dihydroxyphenyl)-beta-aminoethane
Deoxyepinephrine
Dopamin
Dopamina
Dopaminum
Dopastat
Dophamine
Dynatra
Hydroxytyramin
Hydroxytyramine
Intropin
Oxytyramine
Revimine
Revivan

Chemical Formula

C₈H₁₁NO₂

Average Molecular Mass

153.178 g/mol

Monoisotopic Mass

153.079 g/mol

CAS Registry Number

51-61-6

IUPAC Name

4-(2-aminoethyl)benzene-1,2-diol

Traditional Name

dopamine

SMILES

NCCC1=CC(O)=C(O)C=C1

InChI Identifier

InChI=1S/C8H11NO2/c9-4-3-6-1-2-7(10)8(11)5-6/h1-2,5,10-11H,3-4,9H2

InChI Key

InChIKey=VYFYYTLLBUKUHU-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as catecholamines and derivatives. Catecholamines and derivatives are compounds containing 4-(2-Aminoethyl)pyrocatechol [4-(2-aminoethyl)benzene-1,2-diol] or a derivative thereof formed by substitution.

Kingdom

Super Class

Class

Sub Class

Direct Parent

Catecholamines and derivatives

Alternative Parents

Substituents

Catecholamine
Phenethylamine
2-arylethylamine
1-hydroxy-4-unsubstituted benzenoid
1-hydroxy-2-unsubstituted benzenoid
Aralkylamine
Monocyclic benzene moiety
Amine
Hydrocarbon derivative
Primary amine
Organopnictogen compound
Organooxygen compound
Organonitrogen compound
Primary aliphatic amine
Organic oxygen compound
Organic nitrogen compound
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

catecholamine (CHEBI:18243 )
Biogenic amines (C03758 )
Tyramine derivatives (C03758 )
Dopamine (C03758 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Adipose Tissue
Adrenal Cortex
Adrenal Gland
Adrenal Medulla
Bladder
Brain
Epidermis
Fibroblasts
Kidney
Muscle
Myelin
Nerve Cells
Neuron
Pancreas
Placenta
Platelet
Skeletal Muscle
Spleen
Striatum
Testes

Pathways

Name	SMPDB Link	KEGG Link
Catecholamine Biosynthesis	SMP00012	map00350
Tyrosine Metabolism	SMP00006	map00350
Aromatic L-Aminoacid Decarboxylase Deficiency	SMP00170	Not Available
Dopamine beta-hydroxylase deficiency	SMP00498	Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	128°C
Boiling Point	227°C at 2.30E+01 mm Hg
Solubility	600 g/L
LogP	-0.98

Predicted Properties

Property	Value	Source
Water Solubility	7.43 g/L	ALOGPS
logP	-0.4	ALOGPS
logP	0.03	ChemAxon
logS	-1.3	ALOGPS
pKa (Strongest Acidic)	10.01	ChemAxon
pKa (Strongest Basic)	9.27	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	66.48 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	43.25 m³·mol⁻¹	ChemAxon
Polarizability	16.21 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-00di-1900000000-117a1a7207245f5377e7	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (4 TMS)	splash10-00di-1900000000-8b7dcae82868308513da	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-1900000000-117a1a7207245f5377e7	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-00di-1900000000-8b7dcae82868308513da	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-001i-8900000000-752bc8c11fa321b8a7ac	2017-07-27	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-0089-9280000000-c894c19dda88ac048dd4	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_4) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-0uxu-4900000000-ff51177ebcb89b8c956c	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-0006-9200000000-a554eb700a06cecb8292	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-014l-9000000000-db9813e1025f237a549b	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-0udi-0900000000-27e0d71db6d14d79759c	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-0uk9-0900000000-f1cf97c0d0dd509e229e	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-00di-0900000000-aa09a2411e287abe74ed	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-00di-1900000000-97c42b109cab2005373d	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-006x-9700000000-974bd18febffcceea2d6	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-0f79-0900000000-099173d4201beca9e548	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-000i-1900000000-9dc09f2661247c9d84b0	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-0006-9300000000-8b85fa9aac1ffb4c2873	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-0006-9000000000-9ea16d2057010279d433	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-014l-9000000000-32ca2db8fe2b4729ab94	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-0f79-0900000000-ff587935c79b4592ffcf	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-000i-1900000000-8a35d8a2241bc18d6c50	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-0006-9300000000-356a4b8f268863c7893e	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-0006-9000000000-a88c1004f357858fbc6c	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-014l-9000000000-271874005dcb90288512	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-0udi-0900000000-cfa7e1cb9f02ffb4447d	2017-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0udr-0900000000-4e409c6edda911de39fe	2017-06-28	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-000i-1900000000-90aa0e0866454c2eacc7	2017-06-28	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-1000-9400000000-210fd696305d8cf76164	2017-06-28	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udi-0900000000-ff95007680e484d3c57e	2017-06-28	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0udi-1900000000-6dcfecebbd98220ef746	2017-06-28	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0kil-6900000000-f476cfd569c441bc84aa	2017-06-28	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-00e9-8900000000-88acdc978fe4a64e0fc5	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum

Toxicity Profile

Route of Exposure

Dopamine is rapidly absorbed from the small intestine.

Mechanism of Toxicity

Dopamine is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings. In the brain, dopamine actas as an agonist to the five dopamine receptor subtypes (D!, D2, D3, D4, D5).

Metabolism

Biotransformation of dopamine proceeds rapidly to yield the principal excretion products, 3-4-dihydroxy-phenylacetic acid (DOPAC) and 3-methoxy-4-hydroxy-phenylacetic acid (homovanillic acid, HVA). Route of Elimination: It has been reported that about 80% of the drug is excreted in the urine within 24 hours, primarily as HVA and its sulfate and glucuronide conjugates and as 3,4-dihydroxyphenylacetic acid. A very small portion is excreted unchanged. Half Life: 2 minutes

Toxicity Values

LD₅₀ oral mice = 1460 mg/kg, LD₅₀ oral rats = 1780 mg/kg

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

For the correction of hemodynamic imbalances present in the shock syndrome due to myocardial infarction, trauma, endotoxic septicemia, open-heart surgery, renal failure, and chronic cardiac decompensation as in congestive failure

Minimum Risk Level

Not Available

Health Effects

Chronically high levels of dopamine are associated with at least 2 inborn errors of metabolism including: Aromatic L-Amino acid Decarboxylase Deficiency and Norepinephrine deficiency.

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

18243

BioCyc ID

DOPAMINE

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

LDP

ACToR ID

Not Available

Wikipedia Link

Dopamine

References

Synthesis Reference

Klaus Schoellkopf, Rudolf Albrecht, Manfred Lehmann, Gertrud Schroeder, “Novel dopamine derivatives, processes for their preparation, and their use as medicinal agents.” U.S. Patent US4958026, issued February, 1972.

MSDS

Link

General References

Barron AB, Maleszka R, Vander Meer RK, Robinson GE: Octopamine modulates honey bee dance behavior. Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1703-7. Epub 2007 Jan 19. [17237217 ]
Giuliano F, Allard J: Dopamine and male sexual function. Eur Urol. 2001 Dec;40(6):601-8. [11805404 ]
Giuliano F, Allard J: Dopamine and sexual function. Int J Impot Res. 2001 Aug;13 Suppl 3:S18-28. [11477488 ]
Berridge KC, Robinson TE: What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev. 1998 Dec;28(3):309-69. [9858756 ]
Pecina S, Cagniard B, Berridge KC, Aldridge JW, Zhuang X: Hyperdopaminergic mutant mice have higher "wanting" but not "liking" for sweet rewards. J Neurosci. 2003 Oct 15;23(28):9395-402. [14561867 ]
Raskind MA, Peskind ER, Holmes C, Goldstein DS: Patterns of cerebrospinal fluid catechols support increased central noradrenergic responsiveness in aging and Alzheimer's disease. Biol Psychiatry. 1999 Sep 15;46(6):756-65. [10494443 ]
Mannelli M, Ianni L, Lazzeri C, Castellani W, Pupilli C, La Villa G, Barletta G, Serio M, Franchi F: In vivo evidence that endogenous dopamine modulates sympathetic activity in man. Hypertension. 1999 Sep;34(3):398-402. [10489384 ]
Jiang H, Betancourt L, Smith RG: Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers. Mol Endocrinol. 2006 Aug;20(8):1772-85. Epub 2006 Apr 6. [16601073 ]
Brody AL, Mandelkern MA, Olmstead RE, Scheibal D, Hahn E, Shiraga S, Zamora-Paja E, Farahi J, Saxena S, London ED, McCracken JT: Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens. Arch Gen Psychiatry. 2006 Jul;63(7):808-16. [16818870 ]
Bauman A: Unilateral adrenal catecholamine excess. Pheochromocytoma or possible sporadic medullary hyperplasia. Arch Intern Med. 1982 Feb;142(2):377-8. [7059264 ]
Goldstein DS, Eisenhofer G, Kopin IJ: Sources and significance of plasma levels of catechols and their metabolites in humans. J Pharmacol Exp Ther. 2003 Jun;305(3):800-11. Epub 2003 Mar 20. [12649306 ]
King BM: The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol Behav. 2006 Feb 28;87(2):221-44. Epub 2006 Jan 18. [16412483 ]
Cucchi ML, Frattini P, Santagostino G, Preda S, Orecchia G: Catecholamines increase in the urine of non-segmental vitiligo especially during its active phase. Pigment Cell Res. 2003 Apr;16(2):111-6. [12622787 ]
Sjoberg S, Eriksson M, Nordin C: L-thyroxine treatment and neurotransmitter levels in the cerebrospinal fluid of hypothyroid patients: a pilot study. Eur J Endocrinol. 1998 Nov;139(5):493-7. [9849813 ]
Engelborghs S, Marescau B, De Deyn PP: Amino acids and biogenic amines in cerebrospinal fluid of patients with Parkinson's disease. Neurochem Res. 2003 Aug;28(8):1145-50. [12834252 ]
Kobayashi K, Yasuhara T, Agari T, Muraoka K, Kameda M, Ji Yuan W, Hayase H, Matsui T, Miyoshi Y, Shingo T, Date I: Control of dopamine-secretion by Tet-Off system in an in vivo model of parkinsonian rat. Brain Res. 2006 Aug 2;1102(1):1-11. Epub 2006 Jun 27. [16806124 ]
Schenarts PJ, Sagraves SG, Bard MR, Toschlog EA, Goettler CE, Newell MA, Rotondo MF: Low-dose dopamine: a physiologically based review. Curr Surg. 2006 May-Jun;63(3):219-25. [16757377 ]
Piazza O, Zito G, Valente A, Tufano R: Effects of dopamine infusion on forearm blood flow in critical patients. Med Sci Monit. 2006 Feb;12(2):CR90-3. Epub 2006 Jan 26. [16449954 ]
Wang HY, Xiao Y, Han J, Chang XS: Simultaneous determination of dopamine and carvedilol in human serum and urine by first-order derivative fluorometry. Anal Sci. 2005 Nov;21(11):1281-5. [16317894 ]
Elchisak MA, Carlson JH: Assay of free and conjugated catecholamines by high-performance liquid chromatography with electrochemical detection. J Chromatogr. 1982 Dec 10;233:79-88. [7161364 ]
Eklundh T, Eriksson M, Sjoberg S, Nordin C: Monoamine precursors, transmitters and metabolites in cerebrospinal fluid: a prospective study in healthy male subjects. J Psychiatr Res. 1996 May-Jun;30(3):201-8. [8884658 ]
Kopieniak M, Wieczorkiewicz-Plaza A, Maciejewski R: Dopamine activity changes in cerebral cortex in the course of experimental acute pancreatitis. Ann Univ Mariae Curie Sklodowska Med. 2004;59(1):382-6. [16146016 ]
Raw I, Schmidt BJ, Merzel J: Catecholamines and congenital pain insensitivity. Braz J Med Biol Res. 1984;17(3-4):271-9. [6085021 ]
Nikolelis DP, Drivelos DA, Simantiraki MG, Koinis S: An optical spot test for the detection of dopamine in human urine using stabilized in air lipid films. Anal Chem. 2004 Apr 15;76(8):2174-80. [15080725 ]
Eisenhofer G, Aneman A, Friberg P, Hooper D, Fandriks L, Lonroth H, Hunyady B, Mezey E: Substantial production of dopamine in the human gastrointestinal tract. J Clin Endocrinol Metab. 1997 Nov;82(11):3864-71. [9360553 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. 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

Type	Value	Assay Type	Assay Source
Inhibitory	0.124 uM	Not Available	BindingDB 50002316
Inhibitory	0.13 uM	Not Available	BindingDB 50002316
Inhibitory	0.192 uM	Not Available	BindingDB 50002316
Inhibitory	2.34 uM	Not Available	BindingDB 50002316
Inhibitory	4.47 uM	Not Available	BindingDB 50002316
Inhibitory	12 uM	Not Available	BindingDB 50002316
Inhibitory	18.2 uM	Not Available	BindingDB 50002316
Inhibitory	>10 uM	Not Available	BindingDB 50002316
Dissociation	2.5 uM	Not Available	BindingDB 50002316

References

Ostadali MR, Ahangari G, Eslami MB, Razavi A, Zarrindast MR, Ahmadkhaniha HR, Boulhari J: The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74. [17301410 ]
Dolzan V, Plesnicar BK, Serretti A, Mandelli L, Zalar B, Koprivsek J, Breskvar K: Polymorphisms in dopamine receptor DRD1 and DRD2 genes and psychopathological and extrapyramidal symptoms in patients on long-term antipsychotic treatment. Am J Med Genet B Neuropsychiatr Genet. 2007 Sep 5;144B(6):809-15. [17455212 ]
Hoenicka J, Aragues M, Ponce G, Rodriguez-Jimenez R, Jimenez-Arriero MA, Palomo T: From dopaminergic genes to psychiatric disorders. Neurotox Res. 2007 Jan;11(1):61-72. [17449449 ]
da Silva Lobo DS, Vallada HP, Knight J, Martins SS, Tavares H, Gentil V, Kennedy JL: Dopamine genes and pathological gambling in discordant sib-pairs. J Gambl Stud. 2007 Dec;23(4):421-33. Epub 2007 Mar 30. [17394052 ]
Fu W, Shen J, Luo X, Zhu W, Cheng J, Yu K, Briggs JM, Jin G, Chen K, Jiang H: Dopamine D1 receptor agonist and D2 receptor antagonist effects of the natural product (-)-stepholidine: molecular modeling and dynamics simulations. Biophys J. 2007 Sep 1;93(5):1431-41. Epub 2007 Apr 27. [17468175 ]
Brusniak MY, Pearlman RS, Neve KA, Wilcox RE: Comparative molecular field analysis-based prediction of drug affinities at recombinant D1A dopamine receptors. J Med Chem. 1996 Feb 16;39(4):850-9. [8632409 ]
Herm L, Berenyi S, Vonk A, Rinken A, Sipos A: N-Substituted-2-alkyl- and 2-arylnorapomorphines: novel, highly active D2 agonists. Bioorg Med Chem. 2009 Jul 1;17(13):4756-62. doi: 10.1016/j.bmc.2009.04.047. Epub 2009 May 3. [19454369 ]
Michaelides MR, Hong Y, DiDomenico S Jr, Asin KE, Britton DR, Lin CW, Williams M, Shiosaki K: (5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopent-1- ena[c]-phenanthrene-9,10-diol (A-86929): a potent and selective dopamine D1 agonist that maintains behavioral efficacy following repeated administration and characterization of its diacetyl prodrug (ABT-431). J Med Chem. 1995 Sep 1;38(18):3445-7. [7658429 ]
Pettersson I, Liljefors T, Bogeso K: Conformational analysis and structure-activity relationships of selective dopamine D-1 receptor agonists and antagonists of the benzazepine series. J Med Chem. 1990 Aug;33(8):2197-204. [1973733 ]
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 ]
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 ]
Spetea M, Berzetei-Gurske IP, Guerrieri E, Schmidhammer H: Discovery and pharmacological evaluation of a diphenethylamine derivative (HS665), a highly potent and selective kappa opioid receptor agonist. J Med Chem. 2012 Nov 26;55(22):10302-6. doi: 10.1021/jm301258w. Epub 2012 Nov 7. [23134120 ]
Reinart-Okugbeni R, Ausmees K, Kriis K, Werner F, Rinken A, Kanger T: Chemoenzymatic synthesis and evaluation of 3-azabicyclo[3.2.0]heptane derivatives as dopaminergic ligands. Eur J Med Chem. 2012 Sep;55:255-61. doi: 10.1016/j.ejmech.2012.07.025. Epub 2012 Jul 24. [22846798 ]
Wilcox RE, Tseng T, Brusniak MY, Ginsburg B, Pearlman RS, Teeter M, DuRand C, Starr S, Neve KA: CoMFA-based prediction of agonist affinities at recombinant D1 vs D2 dopamine receptors. J Med Chem. 1998 Oct 22;41(22):4385-99. [9784114 ]
Tiberi M, Jarvie KR, Silvia C, Falardeau P, Gingrich JA, Godinot N, Bertrand L, Yang-Feng TL, Fremeau RT Jr, Caron MG: Cloning, molecular characterization, and chromosomal assignment of a gene encoding a second D1 dopamine receptor subtype: differential expression pattern in rat brain compared with the D1A receptor. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7491-5. [1831904 ]
Ryman-Rasmussen JP, Nichols DE, Mailman RB: Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists. Mol Pharmacol. 2005 Oct;68(4):1039-48. Epub 2005 Jun 28. [15985612 ]

Target Details

2. 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

Type	Value	Assay Type	Assay Source
Inhibitory	0.00189 uM	Not Available	BindingDB 50002316
Inhibitory	0.0029 uM	Not Available	BindingDB 50002316
Inhibitory	0.017 uM	Not Available	BindingDB 50002316
Inhibitory	0.11 uM	Not Available	BindingDB 50002316
Inhibitory	0.19 uM	Not Available	BindingDB 50002316
Inhibitory	0.26 uM	Not Available	BindingDB 50002316
Inhibitory	0.36 uM	Not Available	BindingDB 50002316
Inhibitory	0.422 uM	Not Available	BindingDB 50002316
Inhibitory	0.45 uM	Not Available	BindingDB 50002316
Inhibitory	0.572 uM	Not Available	BindingDB 50002316
Inhibitory	0.759 uM	Not Available	BindingDB 50002316
Inhibitory	1.1 uM	Not Available	BindingDB 50002316
Inhibitory	1.9 uM	Not Available	BindingDB 50002316
Inhibitory	2.1 uM	Not Available	BindingDB 50002316
Inhibitory	7.94 uM	Not Available	BindingDB 50002316
IC50	0.000000008 uM	Not Available	BindingDB 50002316

References

Ostadali MR, Ahangari G, Eslami MB, Razavi A, Zarrindast MR, Ahmadkhaniha HR, Boulhari J: The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74. [17301410 ]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Neumeyer JL, Guan JH, Niznik HB, Dumbrille-Ross A, Seeman P, Padmanabhan S, Elmaleh DR: Novel photoaffinity label for the dopamine D2 receptor: synthesis of 4-azido-5-iodo-2-methoxy-N-[1-(phenylmethyl)-4-piperidinyl] benzamide (iodoazidoclebopride, IAC) and the corresponding 125I-labeled analogue (125IAC). J Med Chem. 1985 Apr;28(4):405-7. [3156993 ]
Malmberg A, Hook BB, Johansson AM, Hacksell U: Novel (R)-2-amino-5-fluorotetralins: dopaminergic antagonists and inverse agonists. J Med Chem. 1996 Oct 25;39(22):4421-9. [8893836 ]
Hook BB, Brege C, Linnanen T, Mikaels A, Malmberg A, Johansson AM: Derivatives of (R)-2-amino-5-methoxytetralin: antagonists and inverse agonists at the dopamine D2A receptor. Bioorg Med Chem Lett. 1999 Aug 2;9(15):2167-72. [10465538 ]
Pettersson F, Ponten H, Waters N, Waters S, Sonesson C: Synthesis and evaluation of a set of 4-phenylpiperidines and 4-phenylpiperazines as D2 receptor ligands and the discovery of the dopaminergic stabilizer 4-[3-(methylsulfonyl)phenyl]-1-propylpiperidine (huntexil, pridopidine, ACR16). J Med Chem. 2010 Mar 25;53(6):2510-20. doi: 10.1021/jm901689v. [20155917 ]
Hubner H, Haubmann C, Utz W, Gmeiner P: Conjugated enynes as nonaromatic catechol bioisosteres: synthesis, binding experiments, and computational studies of novel dopamine receptor agonists recognizing preferentially the D(3) subtype. J Med Chem. 2000 Feb 24;43(4):756-62. [10691700 ]
Sanna F, Ortner B, Hubner H, Lober S, Tschammer N, Gmeiner P: Discovery of dopamine D(4) receptor antagonists with planar chirality. Bioorg Med Chem. 2013 Apr 1;21(7):1680-4. doi: 10.1016/j.bmc.2013.01.065. Epub 2013 Feb 5. [23428965 ]
Michaelides MR, Hong Y, DiDomenico S Jr, Asin KE, Britton DR, Lin CW, Williams M, Shiosaki K: (5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopent-1- ena[c]-phenanthrene-9,10-diol (A-86929): a potent and selective dopamine D1 agonist that maintains behavioral efficacy following repeated administration and characterization of its diacetyl prodrug (ABT-431). J Med Chem. 1995 Sep 1;38(18):3445-7. [7658429 ]
Dorfler M, Tschammer N, Hamperl K, Hubner H, Gmeiner P: Novel D3 selective dopaminergics incorporating enyne units as nonaromatic catechol bioisosteres: synthesis, bioactivity, and mutagenesis studies. J Med Chem. 2008 Nov 13;51(21):6829-38. doi: 10.1021/jm800895v. Epub 2008 Oct 4. [18834111 ]
Spetea M, Berzetei-Gurske IP, Guerrieri E, Schmidhammer H: Discovery and pharmacological evaluation of a diphenethylamine derivative (HS665), a highly potent and selective kappa opioid receptor agonist. J Med Chem. 2012 Nov 26;55(22):10302-6. doi: 10.1021/jm301258w. Epub 2012 Nov 7. [23134120 ]
Reinart-Okugbeni R, Ausmees K, Kriis K, Werner F, Rinken A, Kanger T: Chemoenzymatic synthesis and evaluation of 3-azabicyclo[3.2.0]heptane derivatives as dopaminergic ligands. Eur J Med Chem. 2012 Sep;55:255-61. doi: 10.1016/j.ejmech.2012.07.025. Epub 2012 Jul 24. [22846798 ]
Reinart-Okugbeni R, Vonk A, Uustare A, Gyulai Z, Sipos A, Rinken A: 1-substituted apomorphines as potent dopamine agonists. Bioorg Med Chem. 2013 Jul 15;21(14):4143-50. doi: 10.1016/j.bmc.2013.05.014. Epub 2013 May 16. [23727194 ]
Wilcox RE, Tseng T, Brusniak MY, Ginsburg B, Pearlman RS, Teeter M, DuRand C, Starr S, Neve KA: CoMFA-based prediction of agonist affinities at recombinant D1 vs D2 dopamine receptors. J Med Chem. 1998 Oct 22;41(22):4385-99. [9784114 ]
Schiffer WK, Liebling CN, Reiszel C, Hooker JM, Brodie JD, Dewey SL: Cue-induced dopamine release predicts cocaine preference: positron emission tomography studies in freely moving rodents. J Neurosci. 2009 May 13;29(19):6176-85. doi: 10.1523/JNEUROSCI.5221-08.2009. [19439595 ]

Target Details

3. 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

Type	Value	Assay Type	Assay Source
Inhibitory	0.0132 uM	Not Available	BindingDB 50002316
Inhibitory	0.015 uM	Not Available	BindingDB 50002316
Inhibitory	0.02 uM	Not Available	BindingDB 50002316
Inhibitory	0.021 uM	Not Available	BindingDB 50002316
Inhibitory	0.05 uM	Not Available	BindingDB 50002316
Inhibitory	0.072 uM	Not Available	BindingDB 50002316
Inhibitory	0.24 uM	Not Available	BindingDB 50002316
Inhibitory	1.6 uM	Not Available	BindingDB 50002316

References

Ostadali MR, Ahangari G, Eslami MB, Razavi A, Zarrindast MR, Ahmadkhaniha HR, Boulhari J: The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74. [17301410 ]
Malmberg A, Hook BB, Johansson AM, Hacksell U: Novel (R)-2-amino-5-fluorotetralins: dopaminergic antagonists and inverse agonists. J Med Chem. 1996 Oct 25;39(22):4421-9. [8893836 ]
Reinart-Okugbeni R, Ausmees K, Kriis K, Werner F, Rinken A, Kanger T: Chemoenzymatic synthesis and evaluation of 3-azabicyclo[3.2.0]heptane derivatives as dopaminergic ligands. Eur J Med Chem. 2012 Sep;55:255-61. doi: 10.1016/j.ejmech.2012.07.025. Epub 2012 Jul 24. [22846798 ]
Spetea M, Berzetei-Gurske IP, Guerrieri E, Schmidhammer H: Discovery and pharmacological evaluation of a diphenethylamine derivative (HS665), a highly potent and selective kappa opioid receptor agonist. J Med Chem. 2012 Nov 26;55(22):10302-6. doi: 10.1021/jm301258w. Epub 2012 Nov 7. [23134120 ]
Sanna F, Ortner B, Hubner H, Lober S, Tschammer N, Gmeiner P: Discovery of dopamine D(4) receptor antagonists with planar chirality. Bioorg Med Chem. 2013 Apr 1;21(7):1680-4. doi: 10.1016/j.bmc.2013.01.065. Epub 2013 Feb 5. [23428965 ]
Hubner H, Haubmann C, Utz W, Gmeiner P: Conjugated enynes as nonaromatic catechol bioisosteres: synthesis, binding experiments, and computational studies of novel dopamine receptor agonists recognizing preferentially the D(3) subtype. J Med Chem. 2000 Feb 24;43(4):756-62. [10691700 ]
Dorfler M, Tschammer N, Hamperl K, Hubner H, Gmeiner P: Novel D3 selective dopaminergics incorporating enyne units as nonaromatic catechol bioisosteres: synthesis, bioactivity, and mutagenesis studies. J Med Chem. 2008 Nov 13;51(21):6829-38. doi: 10.1021/jm800895v. Epub 2008 Oct 4. [18834111 ]

Target Details

4. 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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0012 uM	Not Available	BindingDB 50002316
Inhibitory	0.0062 uM	Not Available	BindingDB 50002316
Inhibitory	0.015 uM	Not Available	BindingDB 50002316
Inhibitory	0.062 uM	Not Available	BindingDB 50002316
Inhibitory	3.31 uM	Not Available	BindingDB 50002316

References

Ostadali MR, Ahangari G, Eslami MB, Razavi A, Zarrindast MR, Ahmadkhaniha HR, Boulhari J: The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74. [17301410 ]
Hubner H, Haubmann C, Utz W, Gmeiner P: Conjugated enynes as nonaromatic catechol bioisosteres: synthesis, binding experiments, and computational studies of novel dopamine receptor agonists recognizing preferentially the D(3) subtype. J Med Chem. 2000 Feb 24;43(4):756-62. [10691700 ]
Dorfler M, Tschammer N, Hamperl K, Hubner H, Gmeiner P: Novel D3 selective dopaminergics incorporating enyne units as nonaromatic catechol bioisosteres: synthesis, bioactivity, and mutagenesis studies. J Med Chem. 2008 Nov 13;51(21):6829-38. doi: 10.1021/jm800895v. Epub 2008 Oct 4. [18834111 ]
Macchia B, Cervetto L, Demontis GC, Domiano P, Longoni B, Macchia M, Minutolo F, Orlandini E, Ortore G, Papi C: Synthesis and dopaminergic properties of the two enantiomers of 3-(3,4-dimethylphenyl)-1-propylpiperidine, a potent and selective dopamine D4 receptor ligand. Bioorg Med Chem Lett. 2001 Jan 22;11(2):223-6. [11206464 ]
Di Stefano A, Sozio P, Cacciatore I, Cocco A, Giorgioni G, Costa B, Montali M, Lucacchini A, Martini C, Spoto G, Di Pietrantonio F, Di Matteo E, Pinnen F: Preparation and pharmacological characterization of trans-2-amino-5(6)-fluoro-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes as D2-like dopamine receptor agonists. J Med Chem. 2005 Apr 7;48(7):2646-54. [15801855 ]

Target Details

5. Dopamine beta-hydroxylase

General Function:: L-ascorbic acid binding
Specific Function:: Conversion of dopamine to noradrenaline.
Gene Name:: DBH
Uniprot ID:: P09172
Molecular Weight:: 69064.45 Da

References

Goldman JM, Cooper RL, Murr AS: Reproductive functions and hypothalamic catecholamines in response to the soil fumigant metam sodium: adaptations to extended exposures. Neurotoxicol Teratol. 2007 May-Jun;29(3):368-76. Epub 2006 Dec 6. [17258889 ]
Arboleda G, Huang TJ, Waters C, Verkhratsky A, Fernyhough P, Gibson RM: Insulin-like growth factor-1-dependent maintenance of neuronal metabolism through the phosphatidylinositol 3-kinase-Akt pathway is inhibited by C2-ceramide in CAD cells. Eur J Neurosci. 2007 May;25(10):3030-8. [17561816 ]
Garland EM, Black BK, Harris PA, Robertson D: Dopamine-beta-hydroxylase in postural tachycardia syndrome. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H684-90. [17625104 ]
Pyatskowit JW, Prohaska JR: Rodent brain and heart catecholamine levels are altered by different models of copper deficiency. Comp Biochem Physiol C Toxicol Pharmacol. 2007 Mar;145(2):275-81. Epub 2007 Jan 12. [17287146 ]
LeBlanc J, Ducharme MB: Plasma dopamine and noradrenaline variations in response to stress. Physiol Behav. 2007 Jun 8;91(2-3):208-11. Epub 2007 Mar 2. [17433386 ]

Target Details

6. 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

Type	Value	Assay Type	Assay Source
Inhibitory	0.228 uM	Not Available	BindingDB 50002316
Inhibitory	2.44 uM	Not Available	BindingDB 50002316

References

Ostadali MR, Ahangari G, Eslami MB, Razavi A, Zarrindast MR, Ahmadkhaniha HR, Boulhari J: The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74. [17301410 ]
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 ]
Di Stefano A, Sozio P, Cacciatore I, Cocco A, Giorgioni G, Costa B, Montali M, Lucacchini A, Martini C, Spoto G, Di Pietrantonio F, Di Matteo E, Pinnen F: Preparation and pharmacological characterization of trans-2-amino-5(6)-fluoro-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes as D2-like dopamine receptor agonists. J Med Chem. 2005 Apr 7;48(7):2646-54. [15801855 ]

Target Details

7. 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

Type	Value	Assay Type	Assay Source
Inhibitory	8.248 uM	Not Available	BindingDB 50002316

References

Weber JT, Hayataka K, O'Connor MF, Parker KK: Rabbit cerebral cortex 5HT1a receptors. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1997 May;117(1):19-24. [9185324 ]
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

8. 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

Lovenberg TW, Baron BM, de Lecea L, Miller JD, Prosser RA, Rea MA, Foye PE, Racke M, Slone AL, Siegel BW, et al.: A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. Neuron. 1993 Sep;11(3):449-58. [8398139 ]
Shen Y, Monsma FJ Jr, Metcalf MA, Jose PA, Hamblin MW, Sibley DR: Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. J Biol Chem. 1993 Aug 25;268(24):18200-4. [8394362 ]

Target Details

9. Sodium-dependent dopamine transporter

General Function:: Monoamine transmembrane transporter activity
Specific Function:: Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:: SLC6A3
Uniprot ID:: Q01959
Molecular Weight:: 68494.255 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	1.77 uM	Not Available	BindingDB 50002316

References

Ostadali MR, Ahangari G, Eslami MB, Razavi A, Zarrindast MR, Ahmadkhaniha HR, Boulhari J: The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74. [17301410 ]
Pristupa ZB, Wilson JM, Hoffman BJ, Kish SJ, Niznik HB: Pharmacological heterogeneity of the cloned and native human dopamine transporter: disassociation of [3H]WIN 35,428 and [3H]GBR 12,935 binding. Mol Pharmacol. 1994 Jan;45(1):125-35. [8302271 ]

Target Details

10. Sodium-dependent noradrenaline transporter

General Function:: Norepinephrine:sodium symporter activity
Specific Function:: Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:: SLC6A2
Uniprot ID:: P23975
Molecular Weight:: 69331.42 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.323 uM	Not Available	BindingDB 50002316

References

Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS: Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse. 2001 Jan;39(1):32-41. [11071707 ]
Paczkowski FA, Bryan-Lluka LJ, Porzgen P, Bruss M, Bonisch H: Comparison of the pharmacological properties of cloned rat, human, and bovine norepinephrine transporters. J Pharmacol Exp Ther. 1999 Aug;290(2):761-7. [10411589 ]

Target Details

11. 5-hydroxytryptamine receptor 1F

General Function:: Serotonin receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids 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. Signaling inhibits adenylate cyclase activity.
Gene Name:: HTR1F
Uniprot ID:: P30939
Molecular Weight:: 41708.505 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	>30 uM	Not Available	BindingDB 50002316

References

Meltzer PC, McPhee M, Madras BK: Synthesis and biological activity of 2-carbomethoxy-3-catechol-8-azabicyclo[3.2.1]octanes. Bioorg Med Chem Lett. 2003 Nov 17;13(22):4133-7. [14592523 ]

12. D(1) dopamine receptor (Protein Group)

General Function:: G-protein coupled amine receptor activity
Specific Function:: Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Included Proteins:: P21728 , P21918

References

Hubner H, Haubmann C, Utz W, Gmeiner P: Conjugated enynes as nonaromatic catechol bioisosteres: synthesis, binding experiments, and computational studies of novel dopamine receptor agonists recognizing preferentially the D(3) subtype. J Med Chem. 2000 Feb 24;43(4):756-62. [10691700 ]

Target Details

13. Sodium-dependent serotonin transporter

General Function:: Serotonin:sodium symporter activity
Specific Function:: Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:: SLC6A4
Uniprot ID:: P31645
Molecular Weight:: 70324.165 Da

References

Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS: Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse. 2001 Jan;39(1):32-41. [11071707 ]

Target Details

14. Synaptic vesicular amine transporter

General Function:: Monoamine transmembrane transporter activity
Specific Function:: Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis.
Gene Name:: SLC18A2
Uniprot ID:: Q05940
Molecular Weight:: 55712.075 Da

References

Gonzalez AM, Walther D, Pazos A, Uhl GR: Synaptic vesicular monoamine transporter expression: distribution and pharmacologic profile. Brain Res Mol Brain Res. 1994 Mar;22(1-4):219-26. [7912402 ]

Target Details

15. Tyrosine-protein kinase Fyn

General Function:: Protein tyrosine kinase activity
Specific Function:: Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1.
Gene Name:: FYN
Uniprot ID:: P06241
Molecular Weight:: 60761.49 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	>100 uM	Not Available	BindingDB 50002316

References

Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]

Dopamine (T3D4300)

Structure for T3D4300: Dopamine

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