Identification

Name
Amphetamine
Accession Number
DB00182  (APRD00480)
Type
Small Molecule
Groups
Approved, Illicit, Investigational
Description

Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. By mimicking the structures of the catecholamine neurotransmitters, noradrenaline and dopamine, amphetamines modulate monoamine release, reuptake, and signalling within the brain. Although "amphetamine" is used as a descriptor of its own structural class, amphetamine properly refers to a racemic free base composed of equal parts of its two optical antipodes: levo-amphetamine and dextro-amphetamine. Used in the past for the treatment of depression, stress, and for concentration improvement, it is currently available as a prescription drug for the treatment of attention hyperactivity disorder (ADHD), narcolepsy, and as an adjunct in the treatment of exogenous obesity. Amphetamine is also available in a mixed salt/mixed enantiomer form (Adderall), where d-amphetamine and l-amphetamine are available in a ratio of 3:1. It is also available in a prodrug form as lisdexamfetamine.

Structure
Thumb
Synonyms
  • 1-phenyl-2-aminopropane
  • 1-Phenylpropan-2-amin
  • alpha-Methylbenzeneethaneamine
  • alpha-Methylphenylethylamine
  • Amfetamine
  • Amfetaminum
  • Amphetamin
  • Amphetamine
  • beta-Aminopropylbenzene
  • beta-Phenylisopropylamin
  • beta-Phenylisopropylamine
  • Desoxynorephedrine
  • rac-(2R)-1-phenylpropan-2-amine
  • rac-amphetamine
  • α-methylbenzeneethaneamine
  • α-methylphenethylamine
  • β-aminopropylbenzene
  • β-phenylisopropylamine
Product Ingredients
IngredientUNIICASInChI Key
Amphetamine adipateZ58RH02W4M64770-51-0OFCJKOOVFDGTLY-UHFFFAOYSA-N
Amphetamine aspartateH527KAP6L525333-81-7OJNSNSZTGUACNI-VAGRMJETSA-N
Amphetamine aspartate monohydrateO1ZPV620O4851591-76-9DAWXRFCLWKUCNS-MNTSKLTCSA-N
Amphetamine sulfate6DPV8NK46S60-13-9PYHRZPFZZDCOPH-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Adzenys ERSuspension, extended release1.25 mg/1mLOralNeos Therapeutics, Lp2017-09-16Not applicableUs
Adzenys XR-ODTTablet, orally disintegrating6.3 mg/1OralNeos Therapeutics, Lp2016-02-16Not applicableUs
Adzenys XR-ODTTablet, orally disintegrating12.5 mg/1OralNeos Therapeutics, Lp2016-02-16Not applicableUs
Adzenys XR-ODTTablet, orally disintegrating3.1 mg/1OralNeos Therapeutics, Lp2016-02-16Not applicableUs
Adzenys XR-ODTTablet, orally disintegrating18.8 mg/1OralNeos Therapeutics, Lp2016-02-16Not applicableUs
Adzenys XR-ODTTablet, orally disintegrating9.4 mg/1OralNeos Therapeutics, Lp2016-02-16Not applicableUs
Adzenys XR-ODTTablet, orally disintegrating15.7 mg/1OralNeos Therapeutics, Lp2016-02-16Not applicableUs
Dyanavel XRSuspension, extended release2.5 mg/1mLOralTris Pharma, Inc.2015-10-01Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amphetamine SulfateTablet10 mg/1OralWilshire Pharmaceuticals2018-03-29Not applicableUs
Amphetamine SulfateTablet10 mg/1OralAmneal Pharmaceuticals LLC2018-09-28Not applicableUs
Amphetamine SulfateTablet5 mg/1OralWilshire Pharmaceuticals2018-03-29Not applicableUs
Amphetamine SulfateTablet5 mg/1OralAmneal Pharmaceuticals LLC2018-09-28Not applicableUs
EvekeoTablet10 mg/1OralArbor Pharmaceuticals2015-11-01Not applicableUs
EvekeoTablet5 mg/1OralArbor Pharmaceuticals2015-02-012017-09-30Us
EvekeoTablet5 mg/1OralArbor Pharmaceuticals2015-11-01Not applicableUs
EvekeoTablet10 mg/1OralArbor Pharmaceuticals2015-02-012017-10-11Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Act Amphetamine XRAmphetamine aspartate monohydrate (6.25 mg) + Amphetamine sulfate (6.25 mg) + Dextroamphetamine saccharate (6.25 mg) + Dextroamphetamine sulfate (6.25 mg)Capsule, extended releaseOralTeva2015-10-02Not applicableCanada
Act Amphetamine XRAmphetamine aspartate monohydrate (3.75 mg) + Amphetamine sulfate (3.75 mg) + Dextroamphetamine saccharate (3.75 mg) + Dextroamphetamine sulfate (3.75 mg)Capsule, extended releaseOralTeva2015-10-02Not applicableCanada
Act Amphetamine XRAmphetamine aspartate monohydrate (2.5 mg) + Amphetamine sulfate (2.5 mg) + Dextroamphetamine saccharate (2.5 mg) + Dextroamphetamine sulfate (2.5 mg)Capsule, extended releaseOralTeva2015-10-02Not applicableCanada
Act Amphetamine XRAmphetamine aspartate monohydrate (7.5 mg) + Amphetamine sulfate (7.5 mg) + Dextroamphetamine saccharate (7.5 mg) + Dextroamphetamine sulfate (7.5 mg)Capsule, extended releaseOralTeva2015-10-02Not applicableCanada
Act Amphetamine XRAmphetamine aspartate monohydrate (6.25 mg) + Amphetamine sulfate (6.25 mg) + Dextroamphetamine saccharate (6.25 mg) + Dextroamphetamine sulfate (6.25 mg)Capsule, extended releaseOralTeva2015-10-02Not applicableCanada
Act Amphetamine XRAmphetamine aspartate monohydrate (1.25 mg) + Amphetamine sulfate (1.25 mg) + Dextroamphetamine saccharate (1.25 mg) + Dextroamphetamine sulfate (1.25 mg)Capsule, extended releaseOralTeva2015-10-02Not applicableCanada
Act Amphetamine XRAmphetamine aspartate monohydrate (5 mg) + Amphetamine sulfate (5 mg) + Dextroamphetamine saccharate (5 mg) + Dextroamphetamine sulfate (5 mg)Capsule, extended releaseOralTeva2015-10-02Not applicableCanada
Act Amphetamine XRAmphetamine aspartate monohydrate (7.5 mg) + Amphetamine sulfate (7.5 mg) + Dextroamphetamine saccharate (7.5 mg) + Dextroamphetamine sulfate (7.5 mg)Capsule, extended releaseOralTeva2015-10-02Not applicableCanada
Act Amphetamine XRAmphetamine aspartate monohydrate (3.75 mg) + Amphetamine sulfate (3.75 mg) + Dextroamphetamine saccharate (3.75 mg) + Dextroamphetamine sulfate (3.75 mg)Capsule, extended releaseOralTeva2015-10-02Not applicableCanada
Act Amphetamine XRAmphetamine aspartate monohydrate (2.5 mg) + Amphetamine sulfate (2.5 mg) + Dextroamphetamine saccharate (2.5 mg) + Dextroamphetamine sulfate (2.5 mg)Capsule, extended releaseOralTeva2015-10-02Not applicableCanada
Categories
UNII
CK833KGX7E
CAS number
300-62-9
Weight
Average: 135.2062
Monoisotopic: 135.104799421
Chemical Formula
C9H13N
InChI Key
KWTSXDURSIMDCE-UHFFFAOYSA-N
InChI
InChI=1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3
IUPAC Name
1-phenylpropan-2-amine
SMILES
CC(N)CC1=CC=CC=C1

Pharmacology

Indication

For treatment of Attention Deficit Disorder with Hyperactivity (ADDH), narcolepsy, and exogenous obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction for patients refractory to alternative therapy.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

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.

TargetActionsOrganism
ASynaptic vesicular amine transporter
inhibitor
Human
ASodium-dependent dopamine transporter
negative modulator
Human
ACocaine- and amphetamine-regulated transcript protein
agonist
Human
ATrace amine-associated receptor 1
agonist
Human
USodium-dependent noradrenaline transporter
stimulator
Human
UAlpha adrenergic receptor
agonist
Human
UBeta adrenergic receptor
agonist
Human
UD(2) dopamine receptor
binder
Human
UAmine oxidase [flavin-containing] B
inhibitor
Human
USodium-dependent serotonin transporter
binder
Human
AMonoamine oxidase
inhibitor
Human
Avesicular monoamine transporter 2 (VMAT2)Not AvailableHuman
Absorption

Amphetamine forms easily absorbed molecules that are highly lipid soluble. D-amphetamine mean peak plasma concentrations of 44.9 ng/mL occurred at a median time of 5.0 hours after dosing, and L-amphetamine mean peak plasma concentrations of 14.5 ng/mL occurred at a median time of 5.25 hours after dosing.

Volume of distribution
Not Available
Protein binding

15-40%

Metabolism

Amphetamine is reported to be oxidized at the 4 position of the benzene ring to form 4-hydroxyamphetamine, or on the side chain α or β carbons to form alpha-hydroxy-amphetamine or norephedrine, respectively. Norephedrine and 4-hydroxy-amphetamine are both active and each is subsequently oxidized to form 4-hydroxy-norephedrine. Alpha-hydroxy-amphetamine undergoes deamination to form phenylacetone, which ultimately forms benzoic acid and its glucuronide and the glycine conjugate hippuric acid. Although the enzymes involved in amphetamine metabolism have not been clearly defined, CYP2D6 is known to be involved with formation of 4-hydroxy-amphetamine. Since CYP2D6 is genetically polymorphic, population variations in amphetamine metabolism are a possibility.

Route of elimination

With normal urine pHs, approximately half of an administered dose of amphetamine is recoverable in urine as derivatives of alpha-hydroxy-amphetamine and approximately another 30-40% of the dose is recoverable in urine as amphetamine itself. Since amphetamine has a pKa of 9 .9, urinary recovery of amphetamine is highly dependent on pH and urine flow rates. Alkaline urine pHs result in less ionization and reduced renal elimination, and acidic pHs and high flow rates result in increased renal elimination with clearances greater than glomerular filtration rates, indicating the involvement of active secretion.

Half life

The half life for adults in the fasted state was found to be 11.25 hr.

Clearance
Not Available
Toxicity

LD50=180 mg/kg(subcutaneous injection in rat). The most common presenting symptoms seen are agitation, hallucinations, suicidal behaviour, and chest pain.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Amphetamine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Amphetamine is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Amphetamine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Amphetamine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Amphetamine is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Amphetamine is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Amphetamine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Amphetamine is combined with 4-hydroxycoumarin.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of serotonin syndrome can be increased when Amphetamine is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineThe risk or severity of adverse effects can be increased when Amphetamine is combined with 6-O-benzylguanine.
Food Interactions
Not Available

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.

US20020090661
General References
  1. 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. [PubMed:7291243]
  2. Chaudhry IA, Turkanis SA, Karler R: Characteristics of "reverse tolerance" to amphetamine-induced locomotor stimulation in mice. Neuropharmacology. 1988 Aug;27(8):777-81. [PubMed:3216957]
  3. Sax KW, Strakowski SM: Behavioral sensitization in humans. J Addict Dis. 2001;20(3):55-65. [PubMed:11681593]
  4. 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:15955613]
  5. Heal DJ, Smith SL, Gosden J, Nutt DJ: Amphetamine, past and present--a pharmacological and clinical perspective. J Psychopharmacol. 2013 Jun;27(6):479-96. doi: 10.1177/0269881113482532. Epub 2013 Mar 28. [PubMed:23539642]
External Links
Human Metabolome Database
HMDB0014328
KEGG Drug
D07445
KEGG Compound
C07514
PubChem Compound
3007
PubChem Substance
46506414
ChemSpider
13852819
BindingDB
50005246
ChEBI
132233
ChEMBL
CHEMBL405
Therapeutic Targets Database
DAP001146
PharmGKB
PA448408
IUPHAR
2147
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Amphetamine
ATC Codes
N06BA01 — Amfetamine
FDA label
Download (10.4 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceHealthy Volunteers1
0RecruitingOtherCardiovascular System / Hemodynamics1
1CompletedNot AvailableHealthy Volunteers1
1CompletedOtherHealthy Volunteers1
1, 2RecruitingTreatmentDependence, Cocaine1
2CompletedTreatmentAttention Deficit Disorder With Hyperactivity2
2CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
2CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Deficient Emotional Self-Regulation (DESR)1
2CompletedTreatmentStrokes1
2RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Autism Spectrum Conditions/Disorders1
2, 3CompletedTreatmentCognitive Impairments / Disseminated Sclerosis / Impaired Processing Speed1
2, 3CompletedTreatmentDependence, Cocaine1
2, 3RecruitingTreatmentDisseminated Sclerosis1
3Active Not RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
3CompletedTreatmentAttention Deficit Disorder With Hyperactivity1
3CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)2
3RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
4CompletedBasic ScienceEating Disorder1
4CompletedTreatmentAttention Deficit Disorder With Hyperactivity1
4CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)4
4CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Deficient Emotional Self-Regulation (DESR)1
4CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Reading Disability1
4CompletedTreatmentMajor Depressive Disorder (MDD)1
4Not Yet RecruitingHealth Services ResearchExpectancy Versus Pharmacotherapy Effect of Adderall1
4RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)2
4RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Problem Behavior1
Not AvailableActive Not RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)3
Not AvailableCompletedNot AvailableHealthy Volunteers / Nicotine Dependence1
Not AvailableCompletedNot AvailableNicotine Dependence1
Not AvailableCompletedTreatmentAttention Deficit Disorder With Hyperactivity1
Not AvailableCompletedTreatmentStrokes1
Not AvailableUnknown StatusTreatmentMajor Depressive Disorder (MDD)1

Pharmacoeconomics

Manufacturers
  • Lannett co inc
  • Akorn inc
  • Teva pharmaceuticals usa inc
Packagers
  • Barr Pharmaceuticals
  • Cambridge Isotope Laboratories Inc.
  • DSM Corp.
  • Eon Labs
  • GlaxoSmithKline Inc.
  • Lundbeck Inc.
  • Physicians Total Care Inc.
  • Shire Inc.
Dosage forms
FormRouteStrength
Capsule, extended releaseOral
Suspension, extended releaseOral1.25 mg/1mL
Tablet, orally disintegratingOral12.5 mg/1
Tablet, orally disintegratingOral15.7 mg/1
Tablet, orally disintegratingOral18.8 mg/1
Tablet, orally disintegratingOral3.1 mg/1
Tablet, orally disintegratingOral6.3 mg/1
Tablet, orally disintegratingOral9.4 mg/1
CapsuleOral
TabletOral
Suspension, extended releaseOral2.5 mg/1mL
TabletOral10 mg/1
TabletOral5 mg/1
Prices
Unit descriptionCostUnit
Desoxyn 5 mg tablet5.1USD tablet
Dexedrine 15 mg 24 Hour Capsule4.22USD capsule
Dexedrine 10 mg 24 Hour Capsule3.23USD capsule
Dexedrine 5 mg 24 Hour Capsule3.0USD capsule
Dexedrine spansule 15 mg2.45USD each
Dexedrine spansule 10 mg1.91USD each
Dexedrine spansule 5 mg1.91USD each
Amphetamine salts 12.5 mg tablet1.43USD tablet
Amphetamine salts 15 mg tablet1.43USD tablet
Amphetamine salts 7.5 mg tablet1.43USD tablet
Amphetamine salts 10 mg tablet1.37USD tablet
Amphetamine salts 20 mg tablet1.37USD tablet
Amphetamine salts 30 mg tablet1.37USD tablet
Amphetamine salts 5 mg tablet1.37USD tablet
Amphetamine Salt Combo 7.5 mg tablet1.3USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6384020Yes2002-05-072021-01-06Us
USRE42096Yes2011-02-012019-04-21Us
US6605300Yes2003-08-122019-04-21Us
US6322819Yes2001-11-272019-04-21Us
USRE41148Yes2010-02-232019-04-21Us
US8062667No2011-11-222029-03-29Us
US8840924No2014-09-232026-06-05Us
US9017731No2015-04-282032-06-28Us
US8709491No2014-04-292032-06-28Us
US9265737No2016-02-232032-06-28Us
US8747902No2014-06-102027-03-15Us
US8597684No2013-12-032027-03-15Us
US8883217No2014-11-112027-03-15Us
US9675703No2017-06-132027-03-15Us
US9173857No2015-11-032026-05-12Us
US6913768No2005-07-052023-05-24Us
US8846100No2014-09-302029-08-24Us
US10086087No2007-03-152027-03-15Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)Volatizes slowly at room temperatureNot Available
water solubilitySlightlyNot Available
logP1.76HANSCH,C ET AL. (1995)
pKa10.1 (at 20 °C)PERRIN,DD (1965)
Predicted Properties
PropertyValueSource
Water Solubility1.74 mg/mLALOGPS
logP1.85ALOGPS
logP1.8ChemAxon
logS-1.9ALOGPS
pKa (Strongest Basic)10.01ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area26.02 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity43.71 m3·mol-1ChemAxon
Polarizability16.17 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9972
Blood Brain Barrier+0.9565
Caco-2 permeable+0.8395
P-glycoprotein substrateNon-substrate0.7379
P-glycoprotein inhibitor INon-inhibitor0.9519
P-glycoprotein inhibitor IINon-inhibitor0.9859
Renal organic cation transporterNon-inhibitor0.8002
CYP450 2C9 substrateNon-substrate0.8114
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateNon-substrate0.795
CYP450 1A2 substrateNon-inhibitor0.5697
CYP450 2C9 inhibitorNon-inhibitor0.9313
CYP450 2D6 inhibitorInhibitor0.657
CYP450 2C19 inhibitorNon-inhibitor0.8445
CYP450 3A4 inhibitorNon-inhibitor0.8709
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8732
Ames testNon AMES toxic0.93
CarcinogenicityNon-carcinogens0.6869
BiodegradationNot ready biodegradable0.6575
Rat acute toxicity3.2491 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9452
hERG inhibition (predictor II)Non-inhibitor0.9231
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.59 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0006-9000000000-98cd0a725199f943d6cf
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014r-0900000000-8c26eef755113726e527
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0900000000-8cb9815fcd67a6b46f05
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-3900000000-5ec7b13e93ed8e0dc0b5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014u-3900000000-bbb73c900841d90c0ba1
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9400000000-074f0f58bee23b3ea45a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9100000000-96e214b1c073232acc7e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-b6e1299382e4b38f6c4f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-2ed560c4c86538c3e790
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-6ddaf7d40e83a5c70c37
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014u-3900000000-5a23e52436daebe58716
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9500000000-f28704987cc3eacc8917
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9100000000-421879391d3453649aad
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-f8b71db6439096bac2b0
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-270039c50b5f89d9c4ad
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-e84756122a0b431eee74
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-3900000000-20cdadf7c5b742c53087

Taxonomy

Description
This compound 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
Phenylpropanes / Aralkylamines / Organopnictogen compounds / Monoalkylamines / Hydrocarbon derivatives
Substituents
Amphetamine or derivatives / Phenylpropane / Aralkylamine / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Primary amine / Organonitrogen compound / Primary aliphatic amine / Amine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
amphetamines (CHEBI:2679)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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...
Gene Name
SLC18A2
Uniprot ID
Q05940
Uniprot Name
Synaptic vesicular amine transporter
Molecular Weight
55712.075 Da
References
  1. 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:15955613]
  2. 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:7751968]
  3. 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. [PubMed:9648873]
  4. 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. [PubMed:21272013]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Negative modulator
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
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. 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. [PubMed:15602501]
  2. 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. [PubMed:15661631]
  3. 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:15764732]
  4. 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. [PubMed:15795321]
  5. 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. [PubMed:15950014]
  6. Kahlig KM, Binda F, Khoshbouei H, Blakely RD, McMahon DG, Javitch JA, Galli A: Amphetamine induces dopamine efflux through a dopamine transporter channel. Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3495-500. Epub 2005 Feb 22. [PubMed:15728379]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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 respons...
Gene Name
CARTPT
Uniprot ID
Q16568
Uniprot Name
Cocaine- and amphetamine-regulated transcript protein
Molecular Weight
12828.975 Da
References
  1. 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. [PubMed:15597110]
  2. 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. [PubMed:15644956]
  3. 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. [PubMed:15661821]
  4. 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. [PubMed:15680473]
  5. 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. [PubMed:15680478]
  6. Vicentic A, Lakatos A, Jones D: The CART receptors: background and recent advances. Peptides. 2006 Aug;27(8):1934-7. Epub 2006 May 19. [PubMed:16713658]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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 amin...
Gene Name
TAAR1
Uniprot ID
Q96RJ0
Uniprot Name
Trace amine-associated receptor 1
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:15764732]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Stimulator
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
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. 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. [PubMed:12954796]
  2. 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. [PubMed:7700252]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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) prot...

Components:
References
  1. 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. [PubMed:4399738]
  2. 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. [PubMed:6245760]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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 e...

Components:
References
  1. 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. [PubMed:4399738]
  2. 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. [PubMed:6245760]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
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
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. 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. [PubMed:1532675]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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...
Gene Name
MAOB
Uniprot ID
P27338
Uniprot Name
Amine oxidase [flavin-containing] B
Molecular Weight
58762.475 Da
References
  1. 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. [PubMed:7059347]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
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 t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. 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. [PubMed:17209801]
Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin binding
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...

Components:
References
  1. Heal DJ, Smith SL, Gosden J, Nutt DJ: Amphetamine, past and present--a pharmacological and clinical perspective. J Psychopharmacol. 2013 Jun;27(6):479-96. doi: 10.1177/0269881113482532. Epub 2013 Mar 28. [PubMed:23539642]
Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Not Available
Specific Function
Not Available
Gene Name
VMAT2
Uniprot ID
Q99870
Uniprot Name
Vesicle monoamine transporter type 2
Molecular Weight
17291.525 Da
References
  1. Heal DJ, Smith SL, Gosden J, Nutt DJ: Amphetamine, past and present--a pharmacological and clinical perspective. J Psychopharmacol. 2013 Jun;27(6):479-96. doi: 10.1177/0269881113482532. Epub 2013 Mar 28. [PubMed:23539642]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Wu D, Otton SV, Inaba T, Kalow W, Sellers EM: Interactions of amphetamine analogs with human liver CYP2D6. Biochem Pharmacol. 1997 Jun 1;53(11):1605-12. [PubMed:9264312]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Siu EC, Tyndale RF: Selegiline is a mechanism-based inactivator of CYP2A6 inhibiting nicotine metabolism in humans and mice. J Pharmacol Exp Ther. 2008 Mar;324(3):992-9. Epub 2007 Dec 7. [PubMed:18065502]
  3. de la Torre R, Yubero-Lahoz S, Pardo-Lozano R, Farre M: MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant? Front Genet. 2012 Nov 12;3:235. doi: 10.3389/fgene.2012.00235. eCollection 2012. [PubMed:23162568]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Toxin transporter activity
Specific Function
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name
SLC22A3
Uniprot ID
O75751
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
  1. Wu X, Kekuda R, Huang W, Fei YJ, Leibach FH, Chen J, Conway SJ, Ganapathy V: Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998 Dec 4;273(49):32776-86. [PubMed:9830022]
  2. Zhu HJ, Appel DI, Grundemann D, Markowitz JS: Interaction of organic cation transporter 3 (SLC22A3) and amphetamine. J Neurochem. 2010 Jul;114(1):142-9. doi: 10.1111/j.1471-4159.2010.06738.x. Epub 2010 Apr 6. [PubMed:20402963]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter activity
Specific Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. Wu X, Prasad PD, Leibach FH, Ganapathy V: cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun. 1998 May 29;246(3):589-95. [PubMed:9618255]
  2. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V: Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482-92. [PubMed:10454528]
  3. Rytting E, Audus KL: Novel organic cation transporter 2-mediated carnitine uptake in placental choriocarcinoma (BeWo) cells. J Pharmacol Exp Ther. 2005 Jan;312(1):192-8. Epub 2004 Aug 17. [PubMed:15316089]

Drug created on June 13, 2005 07:24 / Updated on November 16, 2018 11:32