T3DB: Amphetamine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (14)XML

Targets (14)

Record Information

Version

2.0

Creation Date

2009-07-21 20:26:14 UTC

Update Date

2014-12-24 20:25:49 UTC

Accession Number

T3D2706

Identification

Common Name

Amphetamine

Class

Small Molecule

Description

Amphetamine is a chiral compound. The racemic mixture can be divided into its optical antipodes: levo- and dextro-amphetamine. Amphetamine is the parent compound of its own structural class, comprising a broad range of psychoactive derivatives, e.g., MDMA (Ecstasy) and the N-methylated form, methamphetamine. Amphetamine is a homologue of phenethylamine.

Compound Type

Adrenergic Agent
Adrenergic Uptake Inhibitor
Amine
Amphetamine
Central Nervous System Stimulant
Dopamine Agent
Dopamine Uptake Inhibitor
Drug
Metabolite
Organic Compound
Sympathomimetic
Synthetic Compound

Chemical Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Synonym
(+/-)-Benzedrine
(+/-)-beta-Phenylisopropylamine
(+/-)-Desoxynorephedrine
1-Methyl-2-phenylethylamine
1-Phenyl-2-aminopropane
1-Phenylpropan-2-amin
3-Methoxyamphetamine
alpha-Methylbenzeneethaneamine
alpha-Methylphenylethylamine
Amfetamine
Amfetaminum
Amphetamin
Amphetamine Sulfate
beta-Aminopropylbenzene
beta-Phenyl-isopropylamine
beta-Phenylisopropylamin
beta-Phenylisopropylamine
Desoxynorephedrine
Dl-1-Phenyl-2-aminopropane
DL-alpha-Methylphenethylamine
Dl-Amphetamine
Dl-Benzedrine
Fenylo-izopropylaminyl
m-Methoxyamphetamine
Methamphetamine HCL
[1-(3-Methoxyphenyl)-2-propyl]amine
α-methylbenzeneethaneamine
α-methylphenethylamine
β-aminopropylbenzene
β-phenylisopropylamine

Chemical Formula

C₉H₁₃N

Average Molecular Mass

135.206 g/mol

Monoisotopic Mass

135.105 g/mol

CAS Registry Number

300-62-9

IUPAC Name

1-phenylpropan-2-amine

Traditional Name

adderall

SMILES

CC(N)CC1=CC=CC=C1

InChI Identifier

InChI=1/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3

InChI Key

InChIKey=KWTSXDURSIMDCE-UHFFFAOYNA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Phenethylamines

Direct Parent

Amphetamines and derivatives

Alternative Parents

Substituents

Amphetamine or derivatives
Phenylpropane
Aralkylamine
Organic nitrogen compound
Organopnictogen compound
Hydrocarbon derivative
Primary amine
Organonitrogen compound
Primary aliphatic amine
Amine
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

amphetamines (CHEBI:2679 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Kidney
Liver

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Volatizes slowly at room temperature
Boiling Point	Not Available
Solubility	Slightly
LogP	1.76

Predicted Properties

Property	Value	Source
Water Solubility	1.74 g/L	ALOGPS
logP	1.85	ALOGPS
logP	1.8	ChemAxon
logS	-1.9	ALOGPS
pKa (Strongest Basic)	10.01	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	1	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	26.02 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	43.71 m³·mol⁻¹	ChemAxon
Polarizability	16.17 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
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0006-9200000000-232318ebc6787ee59036	2017-08-28	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 (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-014r-0900000000-8c26eef755113726e527	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-014i-0900000000-8cb9815fcd67a6b46f05	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-014i-3900000000-5ec7b13e93ed8e0dc0b5	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-014u-3900000000-bbb73c900841d90c0ba1	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-9400000000-074f0f58bee23b3ea45a	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-9100000000-96e214b1c073232acc7e	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-9000000000-b6e1299382e4b38f6c4f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-9000000000-2ed560c4c86538c3e790	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-9000000000-6ddaf7d40e83a5c70c37	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-014u-3900000000-5a23e52436daebe58716	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-9500000000-f28704987cc3eacc8917	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-9100000000-421879391d3453649aad	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-9000000000-f8b71db6439096bac2b0	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-9000000000-270039c50b5f89d9c4ad	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-9000000000-e84756122a0b431eee74	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-014i-3900000000-20cdadf7c5b742c53087	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-014r-0900000000-8c26eef755113726e527	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-014i-0900000000-8cb9815fcd67a6b46f05	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-014i-0900000000-536acc832bfad042e907	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00kr-0900000000-e842cf90085d664ef1c3	2017-07-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-014r-2900000000-2b5fda1ab431107344f5	2017-07-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0fr6-9400000000-b1a9d46f37313e323a64	2017-07-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-001i-1900000000-0e421d19515a1429b103	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-001i-1900000000-fff6e7346b2c36a8ab21	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-014l-7900000000-3cd62c7239479d83b257	2017-07-26	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0006-9000000000-98cd0a725199f943d6cf	2014-09-20	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

Toxicity Profile

Route of Exposure

Oral. Amphetamine forms easily absorbed molecules that are highly lipid soluble.

Mechanism of Toxicity

Amphetamines stimulate the release of norepinephrine from central adrenergic receptors. At higher dosages, they cause release of dopamine from the mesocorticolimbic system and the nigrostriatal dopamine systems. Amphetamine may also act as a direct agonist on central 5-HT receptors and may inhibit monoamine oxidase (MAO). In the periphery, amphetamines are believed to cause the release of noradrenaline by acting on the adrenergic nerve terminals and alpha- and beta-receptors. Modulation of serotonergic pathways may contribute to the calming affect. The drug interacts with VMAT enzymes to enhance release of DA and 5-HT from vesicles. It may also directly cause the reversal of DAT and SERT.

Metabolism

Hepatic Half Life: 10 hours

Toxicity Values

LD50: 180 mg/kg (Subcutaneous, Rat) (4)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

For treatment of Attention Deficit Disorder with Hyperactivity (ADDH) and narcolepsy in children.

Minimum Risk Level

Not Available

Health Effects

Prolonged use may cause hallucinations and intense paranoia. Amphetamines are psychologically addictive. Users who stop using them report that they experience various mood problems such as aggression and anxiety and intense cravings for the drugs. Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.

Symptoms

The most common presenting symptoms seen are agitation, hallucinations, suicidal behaviour, and chest pain.

Treatment

Management of acute amphetamine intoxication is largely symptomatic and includes gastric lavage, administration of activated charcoal, administration of a cathartic and sedation. (8)

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

2679

BioCyc ID

CPD-7659

CTD ID

Not Available

Stitch ID

Amphetamine

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Amphetamine

References

Synthesis Reference

Guohong Wang, “Composition and methods for synthesis of novel tracers for detecting amphetamine and methamphetamine in samples.” U.S. Patent US20020090661, issued July 11, 2002.

MSDS

T3D2706.pdf

General References

Leith NJ, Kuczenski R: Chronic amphetamine: tolerance and reverse tolerance reflect different behavioral actions of the drug. Pharmacol Biochem Behav. 1981 Sep;15(3):399-404. [7291243 ]
Chaudhry IA, Turkanis SA, Karler R: Characteristics of "reverse tolerance" to amphetamine-induced locomotor stimulation in mice. Neuropharmacology. 1988 Aug;27(8):777-81. [3216957 ]
Sax KW, Strakowski SM: Behavioral sensitization in humans. J Addict Dis. 2001;20(3):55-65. [11681593 ]
Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. [15955613 ]
ZAPPI F, MILLEFIORINI M: [Treatment of the antabuse-alcohol complication with betaphenylisopropylamine; experimental aspects]. Riv Neurol. 1955 Sep-Oct;25(5):725-32. [13298508 ]
Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Targets

Target Details

1. 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	0.116 uM	Not Available	BindingDB 50005246

References

Lott DC, Kim SJ, Cook EH Jr, de Wit H: Dopamine transporter gene associated with diminished subjective response to amphetamine. Neuropsychopharmacology. 2005 Mar;30(3):602-9. [15602501 ]
Fone KC, Nutt DJ: Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder. Curr Opin Pharmacol. 2005 Feb;5(1):87-93. [15661631 ]
Miller GM, Verrico CD, Jassen A, Konar M, Yang H, Panas H, Bahn M, Johnson R, Madras BK: Primate trace amine receptor 1 modulation by the dopamine transporter. J Pharmacol Exp Ther. 2005 Jun;313(3):983-94. Epub 2005 Mar 11. [15764732 ]
Garcia BG, Wei Y, Moron JA, Lin RZ, Javitch JA, Galli A: Akt is essential for insulin modulation of amphetamine-induced human dopamine transporter cell-surface redistribution. Mol Pharmacol. 2005 Jul;68(1):102-9. Epub 2005 Mar 28. [15795321 ]
Madras BK, Miller GM, Fischman AJ: The dopamine transporter and attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005 Jun 1;57(11):1397-409. Epub 2005 Jan 5. [15950014 ]
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

2. Cocaine- and amphetamine-regulated transcript protein

General Function:: Not Available
Specific Function:: Satiety factor closely associated with the actions of leptin and neuropeptide y; this anorectic peptide inhibits both normal and starvation-induced feeding and completely blocks the feeding response induced by neuropeptide Y and regulated by leptin in the hypothalamus. It promotes neuronal development and survival in vitro.
Gene Name:: CARTPT
Uniprot ID:: Q16568
Molecular Weight:: 12828.975 Da

References

Loos RJ, Rankinen T, Tremblay A, Perusse L, Chagnon Y, Bouchard C: Melanocortin-4 receptor gene and physical activity in the Quebec Family Study. Int J Obes (Lond). 2005 Apr;29(4):420-8. [15597110 ]
McAlister ED, Van Vugt DA: Effect of leptin administration versus re-feeding on hypothalamic neuropeptide gene expression in fasted male rats. Can J Physiol Pharmacol. 2004 Dec;82(12):1128-34. [15644956 ]
Muhlhausler BS, Adam CL, Marrocco EM, Findlay PA, Roberts CT, McFarlane JR, Kauter KG, McMillen IC: Impact of glucose infusion on the structural and functional characteristics of adipose tissue and on hypothalamic gene expression for appetite regulatory neuropeptides in the sheep fetus during late gestation. J Physiol. 2005 May 15;565(Pt 1):185-95. Epub 2005 Jan 20. [15661821 ]
Scruggs P, Lai CC, Scruggs JE, Dun NJ: Cocaine- and amphetamine-regulated transcript peptide potentiates spinal glutamatergic sympathoexcitation in anesthetized rats. Regul Pept. 2005 Apr 15;127(1-3):79-85. [15680473 ]
Oliveira VX Jr, Fazio MA, Miranda MT, da Silva JM, Bittencourt JC, Elias CF, Miranda A: Leptin fragments induce Fos immunoreactivity in rat hypothalamus. Regul Pept. 2005 Apr 15;127(1-3):123-32. [15680478 ]

Target Details

3. Trace amine-associated receptor 1

General Function:: Trace-amine receptor activity
Specific Function:: Receptor for trace amines, including beta-phenylethylamine (b-PEA), p-tyramine (p-TYR), octopamine and tryptamine, with highest affinity for b-PEA and p-TYR. Unresponsive to classical biogenic amines, such as epinephrine and histamine and only partially activated by dopamine and serotonine. Trace amines are biogenic amines present in very low levels in mammalian tissues. Although some trace amines have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Trace amines are likely to be involved in a variety of physiological functions that have yet to be fully understood. The signal transduced by this receptor is mediated by the G(s)-class of G-proteins which activate adenylate cyclase.
Gene Name:: TAAR1
Uniprot ID:: Q96RJ0
Molecular Weight:: 39091.34 Da

References

Miller GM, Verrico CD, Jassen A, Konar M, Yang H, Panas H, Bahn M, Johnson R, Madras BK: Primate trace amine receptor 1 modulation by the dopamine transporter. J Pharmacol Exp Ther. 2005 Jun;313(3):983-94. Epub 2005 Mar 11. [15764732 ]
Reese EA, Bunzow JR, Arttamangkul S, Sonders MS, Grandy DK: Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and para-hydroxyamphetamine. J Pharmacol Exp Ther. 2007 Apr;321(1):178-86. Epub 2007 Jan 11. [17218486 ]
Xie Z, Westmoreland SV, Bahn ME, Chen GL, Yang H, Vallender EJ, Yao WD, Madras BK, Miller GM: Rhesus monkey trace amine-associated receptor 1 signaling: enhancement by monoamine transporters and attenuation by the D2 autoreceptor in vitro. J Pharmacol Exp Ther. 2007 Apr;321(1):116-27. Epub 2007 Jan 18. [17234900 ]
Wolinsky TD, Swanson CJ, Smith KE, Zhong H, Borowsky B, Seeman P, Branchek T, Gerald CP: The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia. Genes Brain Behav. 2007 Oct;6(7):628-39. Epub 2006 Dec 21. [17212650 ]
Xie Z, Miller GM: Trace amine-associated receptor 1 is a modulator of the dopamine transporter. J Pharmacol Exp Ther. 2007 Apr;321(1):128-36. Epub 2007 Jan 18. [17234899 ]

Target Details

4. 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

Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. [15955613 ]
Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, Ewing A: Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. J Neurosci. 1995 May;15(5 Pt 2):4102-8. [7751968 ]
Teng L, Crooks PA, Dwoskin LP: Lobeline displaces [3H]dihydrotetrabenazine binding and releases [3H]dopamine from rat striatal synaptic vesicles: comparison with d-amphetamine. J Neurochem. 1998 Jul;71(1):258-65. [9648873 ]
Eiden LE, Weihe E: VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse. Ann N Y Acad Sci. 2011 Jan;1216:86-98. doi: 10.1111/j.1749-6632.2010.05906.x. [21272013 ]

5. Alpha adrenergic receptor (Protein Group)

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.
Included Proteins:: P35348 , P35368 , P25100 , P08913 , P18089 , P18825

References

Leibowitz SF: Reciprocal hunger-regulating circuits involving alpha- and beta-adrenergic receptors located, respectively, in the ventromedial and lateral hypothalamus. Proc Natl Acad Sci U S A. 1970 Oct;67(2):1063-70. [4399738 ]
Reisine TD, U'Prichard DC, Wiech NL, Ursillo RC, Yamamura HI: Effects of combined administration of amphetamine and iprindole on brain adrenergic receptors. Brain Res. 1980 Apr 28;188(2):587-92. [6245760 ]

Target Details

6. 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

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]

7. Beta adrenergic receptor (Protein Group)

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.
Included Proteins:: P08588 , P07550 , P13945

References

Leibowitz SF: Reciprocal hunger-regulating circuits involving alpha- and beta-adrenergic receptors located, respectively, in the ventromedial and lateral hypothalamus. Proc Natl Acad Sci U S A. 1970 Oct;67(2):1063-70. [4399738 ]
Reisine TD, U'Prichard DC, Wiech NL, Ursillo RC, Yamamura HI: Effects of combined administration of amphetamine and iprindole on brain adrenergic receptors. Brain Res. 1980 Apr 28;188(2):587-92. [6245760 ]

Target Details

8. 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	0.0071 uM	Not Available	BindingDB 50005246

References

Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R, Glennon RA: In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates. J Pharmacol Exp Ther. 2003 Oct;307(1):138-45. Epub 2003 Sep 3. [12954796 ]
Wall SC, Gu H, Rudnick G: Biogenic amine flux mediated by cloned transporters stably expressed in cultured cell lines: amphetamine specificity for inhibition and efflux. Mol Pharmacol. 1995 Mar;47(3):544-50. [7700252 ]

Target Details

9. 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	6.606 uM	Not Available	BindingDB 50005246

References

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. 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

References

Juhila J, Honkanen A, Sallinen J, Haapalinna A, Korpi ER, Scheinin M: alpha(2A)-Adrenoceptors regulate d-amphetamine-induced hyperactivity and behavioural sensitization in mice. Eur J Pharmacol. 2005 Jul 4;517(1-2):74-83. [15978573 ]

Target Details

11. Amine oxidase [flavin-containing] B

General Function:: Primary amine oxidase activity
Specific Function:: Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
Gene Name:: MAOB
Uniprot ID:: P27338
Molecular Weight:: 58762.475 Da

References

Clarke DE, Lyles GA, Callingham BA: A comparison of cardiac and vascular clorgyline-resistant amine oxidase and monoamine oxidase. Inhibition by amphetamine, mexiletine and other drugs. Biochem Pharmacol. 1982 Jan 1;31(1):27-35. [7059347 ]

Target Details

12. 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	>10 uM	Not Available	BindingDB 50005246

References

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

13. 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

References

Innis RB, Malison RT, al-Tikriti M, Hoffer PB, Sybirska EH, Seibyl JP, Zoghbi SS, Baldwin RM, Laruelle M, Smith EO, et al.: Amphetamine-stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates. Synapse. 1992 Mar;10(3):177-84. [1532675 ]

Target Details

14. 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

Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR: New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol. 2007;47:681-98. [17209801 ]

Amphetamine (T3D2706)

Structure for T3D2706: Amphetamine

Targets

Binding/Activity Constants

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Binding/Activity Constants

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