Lisdexamfetamine

Targets (2)Biointeractions (2)

Identification

Name
Lisdexamfetamine
Accession Number
DB01255
Type
Small Molecule
Groups
Approved, 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
3D
Similar Structures
Synonyms
  • Lisdexamfetamine
  • lisdexamfetamine dimesylate
  • NRP104
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VyvanseCapsule30 mg/1OralShire2007-02-23Not applicableUs
VyvanseCapsule40 mgOralShire Pharma Canada Ulc2010-04-14Not applicableCanada
VyvanseTablet, chewable60 mg/1OralShire2017-01-28Not applicableUs
VyvanseCapsule30 mgOralShire Pharma Canada Ulc2009-08-04Not applicableCanada
VyvanseCapsule20 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2007-12-102014-12-31Us
VyvanseCapsule70 mg/1OralAvera McKennan Hospital2015-09-30Not applicableUs
VyvanseTablet, chewable40 mg/1OralShire2017-01-28Not applicableUs
VyvanseCapsule40 mg/1OralPhysicians Total Care, Inc.2009-03-20Not applicableUs
VyvanseTablet, chewable10 mg/1OralShire2017-01-28Not applicableUs
VyvanseCapsule10 mgOralShire Pharma Canada Ulc2015-06-26Not applicableCanada
Categories
UNII
H645GUL8KJ
CAS number
608137-32-2
Weight
Average: 263.3785
Monoisotopic: 263.199762437
Chemical Formula
C15H25N3O
InChI Key
VOBHXZCDAVEXEY-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

Pharmacology

Indication

For the treatment of Attention Deficit/Hyperactivity Disorder (ADHD) in pediatric populations aged 6 to 12 years.

Associated Conditions
Pharmacodynamics

Lisdexamfetamine 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 action

Lisdexamfetamine 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.

TargetActionsOrganism
ASodium-dependent dopamine transporter
inhibitor
Human
UAlpha-1B adrenergic receptor
antagonist
Human
Absorption

After oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding
Not 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 elimination
Not Available
Half life

The plasma elimination half-life of lisdexamfetamine typically averaged less than one hour.

Clearance
Not Available
Toxicity

Manifestations 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
4-MethoxyamphetamineLisdexamfetamine may decrease the vasoconstricting activities of 4-Methoxyamphetamine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypertensive activities of Lisdexamfetamine.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Lisdexamfetamine.
AcepromazineAcepromazine may increase the antihypertensive activities of Lisdexamfetamine.
AceprometazineAceprometazine may decrease the stimulatory activities of Lisdexamfetamine.
AcetazolamideAcetazolamide may decrease the excretion rate of Lisdexamfetamine which could result in a higher serum level.
AcetophenazineAcetophenazine may decrease the stimulatory activities of Lisdexamfetamine.
AcrivastineLisdexamfetamine may decrease the sedative activities of Acrivastine.
AdrafinilLisdexamfetamine may decrease the vasoconstricting activities of Adrafinil.
AlcaftadineLisdexamfetamine may decrease the sedative activities of Alcaftadine.
Food Interactions
Not 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 References
  1. Jasinski DR, Krishnan S: Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers. J Psychopharmacol. 2009 Jun;23(4):410-8. doi: 10.1177/0269881108093841. Epub 2008 Jul 17. [PubMed:18635707]
  2. Madaan V: Lisdexamfetamine dimesylate for childhood ADHD. Drugs Today (Barc). 2008 May;44(5):319-24. doi: 10.1358/dot.2008.44.5.1215724. [PubMed:18548134]
  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:17035599]
External Links
Human Metabolome Database
HMDB0015385
PubChem Compound
11597698
PubChem Substance
46505358
ChemSpider
9772458
ChEBI
135925
ChEMBL
CHEMBL1201222
Therapeutic Targets Database
DAP000571
PharmGKB
PA164748975
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lisdexamfetamine
ATC Codes
N06BA12 — Lisdexamfetamine
AHFS Codes
  • 28:20.04 — Amphetamines

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentMethamphetamine Dependence1
1CompletedNot AvailableAttention Deficit Disorder With Hyperactivity (ADHD)1
1CompletedNot AvailableHealthy Volunteers2
1CompletedNot AvailableSchizophrenic Disorders1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentDrug Users / Healthy Volunteers1
1CompletedTreatmentHealthy Volunteers1
1TerminatedNot AvailableHealthy Volunteers1
1, 2CompletedBasic ScienceAttention Deficit Disorder With Hyperactivity (ADHD)1
1, 2CompletedTreatmentAmphetamine-Related Disorders / Attention Deficit Disorder With Hyperactivity / Substance-Related Disorders1
1, 2CompletedTreatmentDependence, Cocaine2
2Active Not RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Deficient Emotional Self-Regulation (DESR)1
2CompletedNot AvailableSleep Deprivation1
2CompletedTreatmentAmphetamine-Related Disorders / Attention Deficit Disorder With Hyperactivity / Substance-Related Disorders1
2CompletedTreatmentAttention Deficit Disorder With Hyperactivity1
2CompletedTreatmentBinge Eating Disorder (BED)1
2CompletedTreatmentDependence, Cocaine1
2CompletedTreatmentDisseminated Sclerosis1
2CompletedTreatmentMajor Depressive Disorder (MDD)3
2CompletedTreatmentSchizophrenia and Predominant Negative Symptoms1
2CompletedTreatmentSevere Mood Dysregulation1
2RecruitingNot AvailableBinge Eating Disorder (BED)1
2RecruitingTreatmentAttention Deficit Disorder (ADD) / Attention Deficit Disorder With Hyperactivity (ADHD)1
2RecruitingTreatmentBulimia Nervosa (BN)1
3CompletedNot AvailableAttention Deficit Disorder With Hyperactivity (ADHD)1
3CompletedTreatmentAttention Deficit Disorder (ADD) / Traumatic Brain Injury (TBI)1
3CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)7
3CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Attention Deficit Disorders With Hyperactivity1
3CompletedTreatmentAttention-Deficit/Hyperactivity Disorder1
3CompletedTreatmentBinge Eating Disorder (BED)5
3CompletedTreatmentMajor Depressive Disorder (MDD)2
3RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
3RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Attention-Deficit/Hyperactivity Disorder1
3TerminatedTreatmentBipolar / Depression1
3TerminatedTreatmentDepression, Bipolar1
3TerminatedTreatmentMajor Depressive Disorder (MDD)1
4CompletedNot AvailableAttention Deficit Disorder With Hyperactivity (ADHD)2
4CompletedBasic ScienceAttention Deficit Disorder With Hyperactivity (ADHD)2
4CompletedBasic ScienceAttention Deficit/Hyperactivity Disorder1
4CompletedTreatmentADHD Specifically With Executive Function Impairment1
4CompletedTreatmentAdult Attention Deficit Hyperactivity Disorder (ADHD) With Co-occuring Anxiety and Depressive Disorders1
4CompletedTreatmentAttention Deficit Disorder With Hyperactivity1
4CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)7
4CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Deficient Emotional Self-Regulation (DESR)1
4CompletedTreatmentAttention-Deficit/Hyperactivity Disorder4
4CompletedTreatmentBrain Activity / Cognition / Menopause1
4CompletedTreatmentCognitive Impairments / Myalgic Encephalomyelitis (ME)1
4CompletedTreatmentCognitive Impairments / Symptomatic Menopause1
4CompletedTreatmentMajor Depressive Disorder (MDD)1
4RecruitingOtherLisdexamfetamine1
4RecruitingTreatmentAttention Deficit Disorder (ADD) / Traumatic Brain Injury (TBI)1
4RecruitingTreatmentAttention Deficit Disorder With Hyperactivity1
4RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
4RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Autism Spectrum Conditions/Disorders1
4RecruitingTreatmentCognitive Impairments / RRSO1
4TerminatedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / BMI >30 kg/m2 / Glucose tolerance impaired1
4TerminatedTreatmentDepression, Bipolar1
Not AvailableActive Not RecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)3
Not AvailableCompletedNot AvailableAttention Deficit/Hyperactivity Disorder / Bipolar Disorder (BD)1
Not AvailableCompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
Not AvailableCompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Nicotine Dependence1
Not AvailableCompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD) / Sleep1
Not AvailableNot Yet RecruitingNot AvailableAttention Deficit Disorder With Hyperactivity (ADHD) / Problem Behavior1
Not AvailableNot Yet RecruitingBasic ScienceAttention Deficit Disorder With Hyperactivity (ADHD)1
Not AvailableRecruitingNot AvailableObesity, Morbid1
Not AvailableRecruitingTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
Not AvailableWithdrawnPreventionPlanned RRSO1
Not AvailableWithdrawnTreatmentCognitive Impairments / RRSO1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • New River Pharmaceuticals Inc.
  • Patheon Inc.
  • Physicians Total Care Inc.
  • Quality Care
  • Shire Inc.
Dosage forms
FormRouteStrength
CapsuleOral10 mg/1
CapsuleOral10 mg
CapsuleOral20 mg/1
CapsuleOral20 mg
CapsuleOral30 mg
CapsuleOral30 mg/1
CapsuleOral40 mg
CapsuleOral40 mg/1
CapsuleOral50 mg/1
CapsuleOral50 mg
CapsuleOral60 mg/1
CapsuleOral60 mg
CapsuleOral70 mg/1
CapsuleOral70 mg
Tablet, chewableOral10 mg/1
Tablet, chewableOral20 mg/1
Tablet, chewableOral30 mg/1
Tablet, chewableOral40 mg/1
Tablet, chewableOral50 mg/1
Tablet, chewableOral60 mg/1
Prices
Unit descriptionCostUnit
Vyvanse 30 mg capsule6.24USD capsule
Vyvanse 50 mg capsule6.02USD capsule
Vyvanse 70 mg capsule5.85USD capsule
Vyvanse 40 mg capsule5.8USD capsule
Vyvanse 20 mg capsule5.26USD capsule
Vyvanse 60 mg capsule5.02USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7659253No2003-02-242023-02-24Us
US7718619No2003-02-242023-02-24Us
US7659254No2003-02-242023-02-24Us
US7671030No2003-02-242023-02-24Us
US7662788No2003-02-242023-02-24Us
US7687467No2003-02-242023-02-24Us
US7678770No2003-02-242023-02-24Us
US7671031No2003-02-242023-02-24Us
US7713936No2003-02-242023-02-24Us
US7674774No2003-02-242023-02-24Us
US7678771No2003-02-242023-02-24Us
US7655630No2003-02-242023-02-24Us
US7687466No2003-02-242023-02-24Us
US7223735No2003-02-242023-02-24Us
US7700561No2003-02-242023-02-24Us
US7662787No2003-02-242023-02-24Us
US7723305No2003-02-242023-02-24Us
US7105486No2003-02-242023-02-24Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility792 mg/mL (dimesylate salt)Not Available
logP1.06Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0877 mg/mLALOGPS
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 Area81.14 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity78.31 m3·mol-1ChemAxon
Polarizability31.28 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9858
Blood Brain Barrier+0.9444
Caco-2 permeable+0.664
P-glycoprotein substrateSubstrate0.6919
P-glycoprotein inhibitor INon-inhibitor0.9264
P-glycoprotein inhibitor IINon-inhibitor0.9802
Renal organic cation transporterNon-inhibitor0.8398
CYP450 2C9 substrateNon-substrate0.8303
CYP450 2D6 substrateNon-substrate0.621
CYP450 3A4 substrateNon-substrate0.7228
CYP450 1A2 substrateNon-inhibitor0.7025
CYP450 2C9 inhibitorNon-inhibitor0.9337
CYP450 2D6 inhibitorNon-inhibitor0.858
CYP450 2C19 inhibitorNon-inhibitor0.7568
CYP450 3A4 inhibitorNon-inhibitor0.5499
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8494
Ames testNon AMES toxic0.7156
CarcinogenicityNon-carcinogens0.854
BiodegradationNot ready biodegradable0.8575
Rat acute toxicity2.0058 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9688
hERG inhibition (predictor II)Non-inhibitor0.9004
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid amides
Alternative Parents
Amphetamines and derivatives / Phenylpropanes / N-acyl amines / Secondary carboxylic acid amides / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Alpha-amino acid amide / Amphetamine or derivatives / Phenylpropane / Monocyclic benzene moiety / Fatty amide / Fatty acyl / Benzenoid / N-acyl-amine / Carboxamide group / Secondary carboxylic acid amide
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Details1. Sodium-dependent dopamine transporter
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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. 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. doi: 10.1007/s10519-009-9331-7. Epub 2010 Jan 21. [PubMed:20091113]
Details2. Alpha-1B adrenergic receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
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:17016423]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on May 14, 2007 19:24 / Updated on October 15, 2018 04:36