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Record Information
Version2.0
Creation Date2009-07-21 20:28:52 UTC
Update Date2014-12-24 20:25:56 UTC
Accession NumberT3D3051
Identification
Common NameDextroamphetamine
ClassSmall Molecule
DescriptionDextroamphetamine is only found in individuals that have used or taken this drug. It is the dextrorotary stereoisomer of the amphetamine molecule, which can take two different forms. It is a slightly polar, weak base and is lipophilic. The exact mechanism of action is not known. Dextroamphetamine stimulates the release of norepinephrine from central adrenergic receptors. At higher dosages, it causes release of dopamine from the mesocorticolimbic system and the nigrostriatal dopamine systems by reversal of the monoamine transporters. Dextroamphetamine 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.
Compound Type
  • Adrenergic Agent
  • Adrenergic Uptake Inhibitor
  • Amine
  • Central Nervous System Stimulant
  • Dopamine Agent
  • Dopamine Uptake Inhibitor
  • Drug
  • Metabolite
  • Organic Compound
  • Sympathomimetic
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+)-(S)-amphetamine
(+)-alpha-Methylphenethylamine
(+)-alpha-Methylphenylethylamine
(+)-Amphetamine
(AlphaS)-alpha-methylbenzeneethanamine
(S)-(+)-Amphetamine
(S)-(+)-beta-Phenylisopropylamine
(S)-1-Phenyl-2-aminopropane
(S)-1-Phenyl-2-propylamine
(S)-alpha-Methylbenzeneethanamine
(S)-amphetamine
Attentin
D-Amphetamine
Dexamphetamine
Dexedrine
ProCentra
Zenzedi
Chemical FormulaC9H13N
Average Molecular Mass135.206 g/mol
Monoisotopic Mass135.105 g/mol
CAS Registry Number51-64-9
IUPAC Name(2S)-1-phenylpropan-2-amine
Traditional Nameamphetamine
SMILES[H][C@@](C)(N)CC1=CC=CC=C1
InChI IdentifierInChI=1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3/t8-/m0/s1
InChI KeyInChIKey=KWTSXDURSIMDCE-QMMMGPOBSA-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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenethylamines
Direct ParentAmphetamines 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 FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point< 25°C
Boiling Point203°C
Solubility1.74e+00 g/L
LogP1.76
Predicted Properties
PropertyValueSource
Water Solubility1.74 g/LALOGPS
logP1.85ALOGPS
logP1.8ChemAxon
logS-1.9ALOGPS
pKa (Strongest Basic)10.01ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area26.02 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity43.71 m³·mol⁻¹ChemAxon
Polarizability16.08 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9100000000-41224b447ebed58b4d86JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0006-9000000000-6e32961bde8922a0f2f3JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00kr-0900000000-e842cf90085d664ef1c3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014r-2900000000-2b5fda1ab431107344f5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fr6-9400000000-b1a9d46f37313e323a64JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-1900000000-0e421d19515a1429b103JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-1900000000-fff6e7346b2c36a8ab21JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014l-7900000000-3cd62c7239479d83b257JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00kf-6900000000-4f5d22828acdcb13d83eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-9000000000-c5766ace6b2031302336JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-c8535cbb285cac999590JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-9200000000-0f66be3239e5e65d6028JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9100000000-6720c563d36a88e31cd6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-002f-9000000000-f91f5b5177c2d32668fdJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0006-9000000000-f40d32a5bced4783345aJSpectraViewer | MoNA
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureOral bioavailability is over 75%.
Mechanism of ToxicityThe exact mechanism of action is not known. Dextroamphetamine stimulates the release of norepinephrine from central adrenergic receptors. At higher dosages, it causes release of dopamine from the mesocorticolimbic system and the nigrostriatal dopamine systems by reversal of the monoamine transporters. Dextroamphetamine 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.
MetabolismHepatic. Half Life: 10-28 hours (average is approximately 12 hours)
Toxicity ValuesLD50: 96.8 mg/kg (oral, rat).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed to treat attention deficit hyperactivity disorder (ADHD). Used as a psychostimulant drug. [Wikipedia]
Minimum Risk LevelNot Available
Health EffectsUsing 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.
SymptomsManifestations of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rhabdomyolysis, rapid respiration, hyperpyrexia, confusion, assaultiveness, hallucinations, panic states. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.
TreatmentManagement of acute amphetamine intoxication is largely symptomatic and includes gastric lavage, administration of activated charcoal, administration of a cathartic, and sedation. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendation in this regard. Acidification of the urine increases amphetamine excretion, but is believed to increase risk of acute renal failure if myoglobinuria is present. If acute, severe hypertension complicates amphetamine overdosage, administration of intravenous phentolamine has been suggested. However, a gradual drop in blood pressure will usually result when sufficient sedation has been achieved. Chlorpromazine antagonizes the central stimulant effects of amphetamines and can be used to treat amphetamine intoxication. (11)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01576
HMDB IDHMDB15516
PubChem Compound ID5826
ChEMBL IDCHEMBL612
ChemSpider ID5621
KEGG IDC07884
UniProt IDNot Available
OMIM ID
ChEBI ID4469
BioCyc IDCPD-7658
CTD IDNot Available
Stitch IDDextroamphetamine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkDextroamphetamine
References
Synthesis Reference

Nabenhauer, F.P.; US. Patent 2,276,508; March 17,1942; assigned to Smith, Kline & French
Laboratories.

MSDST3D3051.pdf
General References
  1. Yamada H, Baba T, Hirata Y, Oguri K, Yoshimura H: Studies on N-demethylation of methamphetamine by liver microsomes of guinea-pigs and rats: the role of flavin-containing mono-oxygenase and cytochrome P-450 systems. Xenobiotica. 1984 Nov;14(11):861-6. [6506758 ]
  2. Warneke L: Psychostimulants in psychiatry. Can J Psychiatry. 1990 Feb;35(1):3-10. [2180548 ]
  3. Wagner GJ, Rabkin R: Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial. J Clin Psychiatry. 2000 Jun;61(6):436-40. [10901342 ]
  4. Martinsson L, Yang X, Beck O, Wahlgren NG, Eksborg S: Pharmacokinetics of dexamphetamine in acute stroke. Clin Neuropharmacol. 2003 Sep-Oct;26(5):270-6. [14520168 ]
  5. Butefisch CM, Davis BC, Sawaki L, Waldvogel D, Classen J, Kopylev L, Cohen LG: Modulation of use-dependent plasticity by d-amphetamine. Ann Neurol. 2002 Jan;51(1):59-68. [11782985 ]
  6. Greer CA, Alpern HP: Maturational changes related to dopamine in the effects of d-amphetamine, cocaine, nicotine, and strychnine on seizure susceptibility. Psychopharmacology (Berl). 1979 Sep;64(3):255-60. [116267 ]
  7. Lile JA, Stoops WW, Durell TM, Glaser PE, Rush CR: Discriminative-stimulus, self-reported, performance, and cardiovascular effects of atomoxetine in methylphenidate-trained humans. Exp Clin Psychopharmacol. 2006 May;14(2):136-47. [16756417 ]
  8. Patel JB, Migler B: A sensitive and selective monkey conflict test. Pharmacol Biochem Behav. 1982 Oct;17(4):645-9. [7178177 ]
  9. Chiueh CC, Moore KE: D-amphetamine-induced release of "newly synthesized" and "stored" dopamine from the caudate nucleus in vivo. J Pharmacol Exp Ther. 1975 Mar;192(3):642-53. [1120962 ]
  10. Glick SD, Cox RD, Greenstein S: Relationship of rats' spatial preferences to effects of d-amphetamine on timing behavior. Eur J Pharmacol. 1975 Aug;33(1):173-82. [1236804 ]
  11. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

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
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
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
References
  1. Dlugos A, Freitag C, Hohoff C, McDonald J, Cook EH, Deckert J, de Wit H: Norepinephrine transporter gene variation modulates acute response to D-amphetamine. Biol Psychiatry. 2007 Jun 1;61(11):1296-305. Epub 2007 Jan 17. [17239355 ]
  2. Dlugos AM, Hamidovic A, Palmer AA, de Wit H: Further evidence of association between amphetamine response and SLC6A2 gene variants. Psychopharmacology (Berl). 2009 Oct;206(3):501-11. doi: 10.1007/s00213-009-1628-y. [19727679 ]
  3. Burnette WB, Bailey MD, Kukoyi S, Blakely RD, Trowbridge CG, Justice JB Jr: Human norepinephrine transporter kinetics using rotating disk electrode voltammetry. Anal Chem. 1996 Sep 1;68(17):2932-8. [8794928 ]
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
  1. 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 ]
  2. 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 ]
  3. 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 ]
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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 ]
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
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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 ]
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
References
  1. Zhen J, Chen N, Reith ME: Differences in interactions with the dopamine transporter as revealed by diminishment of Na(+) gradient and membrane potential: dopamine versus other substrates. Neuropharmacology. 2005 Nov;49(6):769-79. Epub 2005 Aug 24. [16122767 ]