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Identification
Name Dextroamphetamine
Accession Number DB01576
Type small molecule
Groups illicit, approved
Description

Dextroamphetamine is the dextrorotary stereoisomer of the amphetamine molecule, which can take two different forms. It is a slightly polar, weak base and is lipophilic.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • (+)-(s)-amphetamine
  • (+)-alpha-methylphenethylamine
  • (+)-alpha-methylphenylethylamine
  • (+)-amphetamine
  • (+)-phenaminum
  • (2S)-(+)-Amphetamine
  • (2S)-1-phenylpropan-2-amine
  • (s)-(+)-amphetamine
  • (s)-(+)-beta-phenylisopropylamine
  • (S)-1-phenyl-2-aminopropane
  • (S)-1-Phenyl-2-propanamine
  • (S)-1-phenyl-2-propylamine
  • (s)-alpha-methylbenzeneethanamine
  • (s)-alpha-methylphenethylamine
  • (s)-alpha-phenylethylamine
  • (s)-amphetamine
  • 1-Methyl-2-phenylethylamine
  • D-(+)-amphetamine
  • D-(s)-amphetamine
  • D-1-Phenyl-2-aminopropan
  • d-1-Phenyl-2-aminopropan [German]
  • D-1-Phenyl-2-aminopropane
  • D-2-Amino-1-phenylpropane
  • D-alpha-methylphenethylamine
  • D-am
  • D-amphetamine
  • Desamfetamina
  • Dexamfetamina [inn-spanish]
  • Dexamfetamine
  • Dexamfetaminum [inn-latin]
  • Dexamphetamine
  • Dexamphetaminum [inn-latin]
  • Dexanfetamina [inn-spanish]
  • Dextroamphetamine
  • Dextroamphetamine sulfate
  • S(+)-amphetamine
Brand names
  • Amsustain
  • Dephadren
  • Desoxyn
  • Dexacaps
  • Dexadrine
  • Dexedrine
  • Dexedrine Spansule
  • Dexidrine
  • Dextrostat
  • Sympamin
Brand name mixtures
  • Adderall XR (Amphetamine Aspartate Monohydrate + Amphetamine Sulfate + Dextroamphetamine Saccharate + Dextroamphetamine Sulfate)
Categories
  • Adrenergic Agents
  • Dopamine Agents
  • Dopamine Uptake Inhibitors
  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
  • Sympathomimetics
CAS number 51-64-9
Weight Average: 135.2062
Monoisotopic: 135.104799421
Chemical Formula C9H13N
InChI Key InChIKey=KWTSXDURSIMDCE-QMMMGPOBSA-N
InChI
InChI=1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3/t8-/m0/s1
Plain Text
IUPAC Name
(2S)-1-phenylpropan-2-amine
SMILES
C[C@H](N)CC1=CC=CC=C1
Plain Text
Mass Spec show (6.9 KB)
Taxonomy
Kingdom Organic
Classes
  • Phenethylamines
  • Amphetamines
Substructures
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Phenethylamines
  • Aromatic compounds
  • Amphetamines
Pharmacology
Indication Used to treat attention deficit hyperactivity disorder (ADHD).
Pharmacodynamics Amphetamines such as dextroamphetamine are noncatecholamine, sympathomimetic amines with CNS stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action. There is neither specific evidence that clearly establishes the mechanism whereby amphetamines produce mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system.
Mechanism of action 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.
Absorption Oral bioavailability is over 75%.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Hepatic.
Route of elimination Not Available
Half life 10-28 hours (average is approximately 12 hours)
Clearance Not Available
Toxicity In rats, the oral LD50 of dextroamphetamine sulfate is 96.8 mg/kg. Manifestations 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.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Smithkline beecham corp dba glaxosmithkline
  • Able laboratories inc
  • Barr laboratories inc
  • Mallinckrodt inc
  • Teva pharmaceuticals usa inc
  • Glaxosmithkline
  • Outlook pharmaceuticals inc
  • Endo pharmaceuticals inc
  • Halsey drug co inc
  • Kv pharmaceutical co
  • Lannett co inc
  • Mm mast and co
  • Purepac pharmaceutical co
  • Sandoz inc
  • Vitarine pharmaceuticals inc
  • Shire development inc
  • Ferndale laboratories inc
Packagers
Dosage forms
Form Route Strength
Capsule, extended release Oral
Tablet Oral
Prices
Unit description Cost Unit
D-amphetamine sulfate powder 900.0 USD g
Desoxyn 5 mg tablet 5.1 USD tablet
Dexedrine 15 mg 24 Hour Capsule 4.22 USD capsule
Dextroamphetamine Sulfate CR 15 mg 24 Hour Capsule 3.47 USD capsule
Dexedrine 10 mg 24 Hour Capsule 3.23 USD capsule
Dexedrine 5 mg 24 Hour Capsule 3.0 USD capsule
Dextroamphetamine Sulfate CR 10 mg 24 Hour Capsule 2.96 USD capsule
Dexedrine spansule 15 mg 2.45 USD each
Dextroamphetamine Sulfate CR 5 mg 24 Hour Capsule 2.06 USD capsule
Dexedrine spansule 10 mg 1.91 USD each
Dexedrine spansule 5 mg 1.91 USD each
Dexedrine 15 mg Sustained-Release Capsule 1.08 USD capsule
Dextroamphetamine Sulfate 10 mg tablet 0.92 USD tablet
Dexedrine 10 mg Sustained-Release Capsule 0.89 USD capsule
Dextroamphetamine Sulfate 5 mg tablet 0.65 USD tablet
Dexedrine 5 mg Tablet 0.62 USD tablet
Dextroamphetamine 10 mg tablet 0.56 USD tablet
Dextrostat 10 mg tablet 0.48 USD tablet
Dextroamphetamine 5 mg tablet 0.28 USD tablet
Dextrostat 5 mg tablet 0.25 USD tablet
Patents Not Available
Properties
State solid
Melting point < 25 oC
Experimental Properties
Property Value Source
logP 1.76 [SANGSTER (1994); similar isomer] PhysProp
Predicted Properties
Property Value Source
water solubility 1.74e+00 g/l ALOGPS
logP 1.85 ALOGPS
logP 1.80 ChemAxon Molconvert
logS -1.89 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 1 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 26.02 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 43.71 ChemAxon Molconvert
polarizability 16.08 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  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. Pubmed
  2. Warneke L: Psychostimulants in psychiatry. Can J Psychiatry. 1990 Feb;35(1):3-10. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
External Links
Resource Link
KEGG Drug D03740 Link_out
KEGG Compound C07884 Link_out
PubChem Compound 5826 Link_out
PubChem Substance 46506252 Link_out
ChemSpider 5621 Link_out
ChEBI 4469 Link_out
ChEMBL 4469 Link_out
Therapeutic Targets Database DAP001470 Link_out
Drug Product Database 1924516 Link_out
RxList http://www.rxlist.com/cgi/generic/dextroamphetamine.htm Link_out
Drugs.com http://www.drugs.com/cdi/dextroamphetamine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Dextroamphetamine Link_out
ATC Codes
  • N06BA02
AHFS Codes
  • 28:20.04
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Synaptic vesicular amine transporter

Pharmacological action: yes
Actions: inducer

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

Organism class: human
UniProt ID: Q05940 Link_out
Gene: SLC18A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed

2. Sodium-dependent noradrenaline transporter

Pharmacological action: yes
Actions: negative modulator

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P23975 Link_out
Gene: SLC6A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Pubmed

3. Sodium-dependent dopamine transporter

Pharmacological action: yes
Actions: negative modulator

Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: Q01959 Link_out
Gene: SLC6A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  2. Kuczenski R, Segal DS, Cho AK, Melega W: Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine. J Neurosci. 1995 Feb;15(2):1308-17. Pubmed
  3. Rothman RB, Dersch CM, Ananthan S, Partilla JS: Studies of the biogenic amine transporters. 13. Identification of “agonist” and “antagonist” allosteric modulators of amphetamine-induced dopamine release. J Pharmacol Exp Ther. 2009 May;329(2):718-28. Epub 2009 Feb 24. Pubmed

4. Trace amine-associated receptor 1

Pharmacological action: unknown
Actions: agonist

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

Organism class: human
UniProt ID: Q96RJ0 Link_out
Gene: TAAR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

5. Alpha-1A adrenergic receptor

Pharmacological action: unknown

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

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

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  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. Pubmed

6. Alpha-1B adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

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

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

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  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. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on August 29, 2007 08:50 / Updated on January 22, 2011 08:35

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.