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Trials

Economics

Properties

Spectra

Taxonomy

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

Similar Structures

Synonyms

Lisdexamfetamine
lisdexamfetamine dimesylate
NRP104

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Vyvanse	Capsule	50 mg/1	Oral	Shire	2007-02-23	Not applicable
Vyvanse	Tablet, chewable	40 mg/1	Oral	Shire	2017-01-28	Not applicable
Vyvanse	Capsule	30 mg	Oral	Shire Pharma Canada Ulc	2009-08-04	Not applicable
Vyvanse	Capsule	10 mg/1	Oral	Avera McKennan Hospital	2015-03-26	2018-06-07
Vyvanse	Capsule	70 mg	Oral	Shire Pharma Canada Ulc	2017-01-05	Not applicable
Vyvanse	Capsule	20 mg	Oral	Shire Pharma Canada Ulc	2010-04-13	Not applicable
Vyvanse	Capsule	10 mg/1	Oral	Shire	2014-08-30	Not applicable
Vyvanse	Capsule	40 mg/1	Oral	Physicians Total Care, Inc.	2009-03-20	Not applicable
Vyvanse	Capsule	70 mg/1	Oral	Shire	2007-02-23	Not applicable
Vyvanse	Tablet, chewable	60 mg/1	Oral	Shire	2017-01-28	Not applicable

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.

Target	Actions	Organism
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

Drug	Interaction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid	The risk or severity of hypertension can be increased when Lisdexamfetamine is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazole	The risk or severity of hypertension can be increased when Lisdexamfetamine is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamine	The risk or severity of serotonin syndrome can be increased when Lisdexamfetamine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine	The risk or severity of serotonin syndrome can be increased when Lisdexamfetamine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthine	The risk or severity of adverse effects can be increased when Lisdexamfetamine is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,4-Methylenedioxyamphetamine	The risk or severity of serotonin syndrome can be increased when Lisdexamfetamine is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamine	The risk or severity of serotonin syndrome can be increased when Lisdexamfetamine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-Methoxyamphetamine	The risk or severity of hypertension can be increased when Lisdexamfetamine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine	The risk or severity of serotonin syndrome can be increased when Lisdexamfetamine is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanine	The risk or severity of adverse effects can be increased when Lisdexamfetamine is combined with 6-O-benzylguanine.

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

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]
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]
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

Phase	Status	Purpose	Conditions	Count
1	Active Not Recruiting	Treatment	Methamphetamine Dependence	1
1	Completed	Not Available	Attention Deficit Disorder With Hyperactivity (ADHD)	1
1	Completed	Not Available	Healthy Volunteers	2
1	Completed	Not Available	Schizophrenic Disorders	1
1	Completed	Basic Science	Healthy Volunteers	1
1	Completed	Treatment	Drug Users / Healthy Volunteers	1
1	Completed	Treatment	Healthy Volunteers	1
1	Terminated	Not Available	Healthy Volunteers	1
1, 2	Completed	Basic Science	Attention Deficit Disorder With Hyperactivity (ADHD)	1
1, 2	Completed	Treatment	Amphetamine-Related Disorders / Attention Deficit Disorder With Hyperactivity / Substance-Related Disorders	1
1, 2	Completed	Treatment	Dependence, Cocaine	2
2	Completed	Not Available	Sleep Deprivation	1
2	Completed	Treatment	Amphetamine-Related Disorders / Attention Deficit Disorder With Hyperactivity / Substance-Related Disorders	1
2	Completed	Treatment	Attention Deficit Disorder With Hyperactivity	1
2	Completed	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD) / Deficient Emotional Self-Regulation (DESR)	1
2	Completed	Treatment	Binge Eating Disorder (BED)	1
2	Completed	Treatment	Dependence, Cocaine	1
2	Completed	Treatment	Disseminated Sclerosis	1
2	Completed	Treatment	Major Depressive Disorder (MDD)	3
2	Completed	Treatment	Schizophrenia and Predominant Negative Symptoms	1
2	Completed	Treatment	Severe Mood Dysregulation	1
2	Recruiting	Not Available	Binge Eating Disorder (BED)	1
2	Recruiting	Treatment	Attention Deficit Disorder (ADD) / Attention Deficit Disorder With Hyperactivity (ADHD)	1
2	Recruiting	Treatment	Bulimia Nervosa (BN)	1
3	Completed	Not Available	Attention Deficit Disorder With Hyperactivity (ADHD)	1
3	Completed	Treatment	Attention Deficit Disorder (ADD) / Traumatic Brain Injury (TBI)	1
3	Completed	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD)	7
3	Completed	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD) / Attention Deficit Disorders With Hyperactivity	1
3	Completed	Treatment	Attention-Deficit/Hyperactivity Disorder	1
3	Completed	Treatment	Binge Eating Disorder (BED)	5
3	Completed	Treatment	Major Depressive Disorder (MDD)	2
3	Recruiting	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD)	1
3	Recruiting	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD) / Attention-Deficit/Hyperactivity Disorder	1
3	Terminated	Treatment	Bipolar / Depression	1
3	Terminated	Treatment	Depression, Bipolar	1
3	Terminated	Treatment	Major Depressive Disorder (MDD)	1
4	Completed	Not Available	Attention Deficit Disorder With Hyperactivity (ADHD)	2
4	Completed	Basic Science	Attention Deficit Disorder With Hyperactivity (ADHD)	2
4	Completed	Basic Science	Attention Deficit/Hyperactivity Disorder	1
4	Completed	Treatment	ADHD Specifically With Executive Function Impairment	1
4	Completed	Treatment	Adult Attention Deficit Hyperactivity Disorder (ADHD) With Co-occuring Anxiety and Depressive Disorders	1
4	Completed	Treatment	Attention Deficit Disorder With Hyperactivity	1
4	Completed	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD)	7
4	Completed	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD) / Deficient Emotional Self-Regulation (DESR)	1
4	Completed	Treatment	Attention-Deficit/Hyperactivity Disorder	4
4	Completed	Treatment	Brain Activity / Cognition / Menopause	1
4	Completed	Treatment	Cognitive Impairments / Myalgic Encephalomyelitis (ME)	1
4	Completed	Treatment	Cognitive Impairments / Symptomatic Menopause	1
4	Completed	Treatment	Major Depressive Disorder (MDD)	1
4	Recruiting	Other	Lisdexamfetamine	1
4	Recruiting	Treatment	Attention Deficit Disorder (ADD) / Traumatic Brain Injury (TBI)	1
4	Recruiting	Treatment	Attention Deficit Disorder With Hyperactivity	1
4	Recruiting	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD)	1
4	Recruiting	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD) / Autism Spectrum Conditions/Disorders	1
4	Recruiting	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD) / Problem Behavior	1
4	Recruiting	Treatment	Cognitive Impairments / RRSO	1
4	Terminated	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD) / BMI >30 kg/m2 / Glucose tolerance impaired	1
4	Terminated	Treatment	Depression, Bipolar	1
Not Available	Active Not Recruiting	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD)	3
Not Available	Completed	Not Available	Attention Deficit/Hyperactivity Disorder / Bipolar Disorder (BD)	1
Not Available	Completed	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD)	1
Not Available	Completed	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD) / Nicotine Dependence	1
Not Available	Completed	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD) / Sleep	1
Not Available	Not Yet Recruiting	Basic Science	Attention Deficit Disorder With Hyperactivity (ADHD)	1
Not Available	Recruiting	Not Available	Obesity, Morbid	1
Not Available	Recruiting	Treatment	Attention Deficit Disorder With Hyperactivity (ADHD)	1
Not Available	Withdrawn	Prevention	Planned RRSO	1
Not Available	Withdrawn	Treatment	Cognitive Impairments / RRSO	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

New River Pharmaceuticals Inc.
Patheon Inc.
Physicians Total Care Inc.
Quality Care
Shire Inc.

Dosage forms

Form	Route	Strength
Capsule	Oral	10 mg/1
Capsule	Oral	10 mg
Capsule	Oral	20 mg/1
Capsule	Oral	20 mg
Capsule	Oral	30 mg
Capsule	Oral	30 mg/1
Capsule	Oral	40 mg
Capsule	Oral	40 mg/1
Capsule	Oral	50 mg/1
Capsule	Oral	50 mg
Capsule	Oral	60 mg/1
Capsule	Oral	60 mg
Capsule	Oral	70 mg/1
Capsule	Oral	70 mg
Tablet, chewable	Oral	10 mg/1
Tablet, chewable	Oral	20 mg/1
Tablet, chewable	Oral	30 mg/1
Tablet, chewable	Oral	40 mg/1
Tablet, chewable	Oral	50 mg/1
Tablet, chewable	Oral	60 mg/1

Prices

Unit description	Cost	Unit
Vyvanse 30 mg capsule	6.24USD	capsule
Vyvanse 50 mg capsule	6.02USD	capsule
Vyvanse 70 mg capsule	5.85USD	capsule
Vyvanse 40 mg capsule	5.8USD	capsule
Vyvanse 20 mg capsule	5.26USD	capsule
Vyvanse 60 mg capsule	5.02USD	capsule

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US7659253	No	2010-02-09	2023-02-24
US7718619	No	2010-05-18	2023-02-24
US7659254	No	2010-02-09	2023-02-24
US7671030	No	2010-03-02	2023-02-24
US7662788	No	2010-02-16	2023-02-24
US7687467	No	2010-03-30	2023-02-24
US7678770	No	2010-03-16	2023-02-24
US7671031	No	2010-03-02	2023-02-24
US7713936	No	2010-05-11	2023-02-24
US7674774	No	2010-03-09	2023-02-24
US7678771	No	2010-03-16	2023-02-24
US7655630	No	2010-02-02	2023-02-24
US7687466	No	2010-03-30	2023-02-24
US7223735	No	2007-05-29	2023-02-24
US7700561	No	2010-04-20	2023-02-24
US7662787	No	2010-02-16	2023-02-24
US7723305	No	2010-05-25	2023-02-24
US7105486	No	2006-09-12	2023-02-24

Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	792 mg/mL (dimesylate salt)	Not Available
logP	1.06	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0877 mg/mL	ALOGPS
logP	1.01	ALOGPS
logP	1.14	ChemAxon
logS	-3.5	ALOGPS
pKa (Strongest Acidic)	15.89	ChemAxon
pKa (Strongest Basic)	10.21	ChemAxon
Physiological Charge	2	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	81.14 Å²	ChemAxon
Rotatable Bond Count	8	ChemAxon
Refractivity	78.31 m³·mol^-1	ChemAxon
Polarizability	31.28 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

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 inhibitor	Non-inhibitor	0.9337
CYP450 2D6 inhibitor	Non-inhibitor	0.858
CYP450 2C19 inhibitor	Non-inhibitor	0.7568
CYP450 3A4 inhibitor	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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not 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

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

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]
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 December 14, 2018 16:27

Lisdexamfetamine

Identification

Structure for Lisdexamfetamine (DB01255)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References