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Identification
NameLisdexamfetamine
Accession NumberDB01255
Typesmall molecule
Groupsapproved, investigational
Description

Lisdexamfetamine (L-lysine-d-amphetamine) is a prodrug of the psychostimulant d-amphetamine coupled with the essential amino acid L-lysine. It was developed so that the amphetamine psychostimulant is released and activated more slowly as the prodrug molecule is hydrolyzed consequently cleaving off the amino acid-during the first pass through the intestines and/or the liver. Amphetamines target the trace amine-associated receptor 1 (TAAR1). Amphetamine is also believed to exert its effects by binding to the monoamine transporters (the dopamine transporter or DAT) and increasing extracellular levels of the biogenic amines dopamine, norepinephrine (noradrenaline) and serotonin.

Structure
Thumb
Synonyms
SynonymLanguageCode
LisdexamfetamineNot AvailableNot Available
lisdexamfetamine dimesylateNot AvailableNot Available
NRP104Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
VyvanseNew River Pharmaceuticals Inc.
Brand mixturesNot Available
CategoriesNot Available
CAS number608137-32-2
WeightAverage: 263.3785
Monoisotopic: 263.199762437
Chemical FormulaC15H25N3O
InChI KeyVOBHXZCDAVEXEY-JSGCOSHPSA-N
InChI
InChI=1S/C15H25N3O/c1-12(11-13-7-3-2-4-8-13)18-15(19)14(17)9-5-6-10-16/h2-4,7-8,12,14H,5-6,9-11,16-17H2,1H3,(H,18,19)/t12-,14-/m0/s1
IUPAC Name
(2S)-2,6-diamino-N-[(2S)-1-phenylpropan-2-yl]hexanamide
SMILES
C[C@@H](CC1=CC=CC=C1)NC(=O)[C@@H](N)CCCCN
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentAlpha Amino Acid Amides
Alternative parentsN-acyl Amines; Amphetamines and Derivatives; Secondary Carboxylic Acid Amides; Polyamines; Carboxylic Acids; Enolates; Monoalkylamines
Substituentsamphetamine or derivative; benzene; carboxamide group; secondary carboxylic acid amide; carboxylic acid; enolate; polyamine; primary aliphatic amine; amine; primary amine; organonitrogen compound
Classification descriptionThis compound belongs to the alpha amino acid amides. These are amide derivatives of alpha amino acids.
Pharmacology
IndicationFor the treatment of Attention Deficit/Hyperactivity Disorder (ADHD) in pediatric populations aged 6 to 12 years.
PharmacodynamicsLisdexamfetamine is a pro-drug of dextroamphetamine. It works primarily by inducing the release of the neurotransmitters dopamine and norepinephrine from their storage areas in nerve terminals. Both of these transmitters contribute to maintaining alertness, increasing focus, and sustaining thought, effort, and motivation.
Mechanism of actionLisdexamfetamine is a pro-drug of dextroamphetamine. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. Norepinephrine and dopamine contribute to maintaining alertness, increasing focus, and sustaining thought, effort, and motivation. However, the exact therapeutic action in ADHD is not known.
AbsorptionAfter oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Lisdexamfetamine is converted to dextroamphetamine and L-lysine, which is believed to occur by first-pass intestinal and/or hepatic metabolism. Lisdexamfetamine is not metabolized by cytochrome P450 enzymes.

Route of eliminationNot Available
Half lifeThe plasma elimination half-life of lisdexamfetamine typically averaged less than one hour.
ClearanceNot Available
ToxicityManifestations of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia and rhabdomyolysis. Fatigue and depression usually follow the central nervous system 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9858
Blood Brain Barrier + 0.9444
Caco-2 permeable + 0.664
P-glycoprotein substrate Substrate 0.6919
P-glycoprotein inhibitor I Non-inhibitor 0.9264
P-glycoprotein inhibitor II Non-inhibitor 0.9802
Renal organic cation transporter Non-inhibitor 0.8398
CYP450 2C9 substrate Non-substrate 0.8303
CYP450 2D6 substrate Non-substrate 0.621
CYP450 3A4 substrate Non-substrate 0.7228
CYP450 1A2 substrate Non-inhibitor 0.7025
CYP450 2C9 substrate Non-inhibitor 0.9337
CYP450 2D6 substrate Non-inhibitor 0.858
CYP450 2C19 substrate Non-inhibitor 0.7568
CYP450 3A4 substrate Non-inhibitor 0.5499
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8494
Ames test Non AMES toxic 0.7156
Carcinogenicity Non-carcinogens 0.854
Biodegradation Not ready biodegradable 0.8575
Rat acute toxicity 2.0058 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9688
hERG inhibition (predictor II) Non-inhibitor 0.9004
Pharmacoeconomics
Manufacturers
  • Shire development inc
  • Shire US Inc
Packagers
Dosage forms
FormRouteStrength
Capsule, extended releaseOral
Prices
Unit descriptionCostUnit
Vyvanse 30 mg capsule6.24USDcapsule
Vyvanse 50 mg capsule6.02USDcapsule
Vyvanse 70 mg capsule5.85USDcapsule
Vyvanse 40 mg capsule5.8USDcapsule
Vyvanse 20 mg capsule5.26USDcapsule
Vyvanse 60 mg capsule5.02USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States71054862003-06-292023-06-29
United States76556302003-02-242023-02-24
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubility792 mg/mL (dimesylate salt)Not Available
logP1.06Not Available
Predicted Properties
PropertyValueSource
water solubility8.77e-02 g/lALOGPS
logP1.01ALOGPS
logP1.14ChemAxon
logS-3.5ALOGPS
pKa (strongest acidic)15.89ChemAxon
pKa (strongest basic)10.21ChemAxon
physiological charge2ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count3ChemAxon
polar surface area81.14ChemAxon
rotatable bond count8ChemAxon
refractivity78.31ChemAxon
polarizability31.28ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Michael J. Bauer, Gary Richard Callen, Judi Christine Humphrey, Todd Jeffrey Johnson, Matthew Wendell Schiesher, “Methods and Compositions for Preparing Lisdexamfetamine and Salts Thereof.” U.S. Patent US20120157706, issued June 21, 2012.

US20120157706
General Reference
  1. Jasinski DR, Krishnan S: Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers. J Psychopharmacol. 2008 Jul 17. Pubmed
  2. Madaan V: Lisdexamfetamine dimesylate for childhood ADHD. Drugs Today (Barc). 2008 May;44(5):319-24. Pubmed
  3. Krishnan S, Moncrief S: An evaluation of the cytochrome p450 inhibition potential of lisdexamfetamine in human liver microsomes. Drug Metab Dispos. 2007 Jan;35(1):180-4. Epub 2006 Oct 11. Pubmed
External Links
ResourceLink
PubChem Compound11597698
PubChem Substance46505358
ChemSpider9772458
Therapeutic Targets DatabaseDAP000571
PharmGKBPA164748975
RxListhttp://www.rxlist.com/cgi/generic/vyvanse.htm
Drugs.comhttp://www.drugs.com/cdi/lisdexamfetamine.html
WikipediaLisdexamfetamine
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
TramadolIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TrandolaprilLisdexamfetamine may reduce the efficacy of Trandolapril.
TranylcypromineThe MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Lisdexamfetamine. Concomitant therapy should be avoided.
TriprolidineTriprolidine may reduce the sedative effect of the antihistamine, Lisdexamfetamine.
Food InteractionsNot Available

Targets

1. Sodium-dependent dopamine transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent dopamine transporter Q01959 Details

References:

  1. Hamidovic A, Dlugos A, Palmer AA, de Wit H: Polymorphisms in dopamine transporter (SLC6A3) are associated with stimulant effects of D-amphetamine: an exploratory pharmacogenetic study using healthy volunteers. Behav Genet. 2010 Mar;40(2):255-61. Epub 2010 Jan 21. Pubmed

2. Alpha-1B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1B adrenergic receptor P35368 Details

References:

  1. 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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

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Drug created on May 14, 2007 19:24 / Updated on September 16, 2013 17:13