LISDEXAMFETAMINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H25N3O
Molecular Weight	263.3785
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

C[C@@H](CC1=CC=CC=C1)NC(=O)[C@@H](N)CCCCN

InChI

InChIKey=VOBHXZCDAVEXEY-JSGCOSHPSA-N

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

HIDE SMILES / InChI

Molecular Formula	C15H25N3O
Molecular Weight	263.3785
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Lisdexamfetamine (LDX) is a d-amphetamine (d-AMPH) pro-drug used to treat Attention Deficit and Hyperactivity Disorder (ADHD) and Binge Eating Disorder (BED). After oral administration, lisdexamfetamine dimesylate is rapidly absorbed from the gastrointestinal tract and converted to dextroamphetamine, which is responsible for the drug’s activity. 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. Most common adverse reactions in children, adolescents and/or adults with ADHD were anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, and vomiting. Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels. Needs to adjust Lisdexamfetamine dosage accordingly.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
catecholamine secretion 14	Modulator 828
Norepinephrine transporter 191	Modulator 828
Synaptic vesicular amine transporter 57	Inhibitor 8,297
Dopamine transporter 180	Modulator 828

Conditions

Condition	Modality	Highest Phase	Product
Attention deficit hyperactivity disorder 68	Primary	Approved 8,429	VYVANSE
Moderate to severe binge eating disorder 12	Primary	Approved 8,429	VYVANSE
Attention deficit hyperactivity disorder 68	Primary	Approved 8,429	DEXEDRINE

C_max

Value	Dose	Analyte	Population
47.9 ng/mL	70 mg 1 times / day multiple, oral	LISDEXAMFETAMINE plasma	Homo sapiens
24.7 ng/mL	10 mg single, oral	DEXTROAMPHETAMINE plasma	Homo sapiens
36.6 ng/mL	15 mg single, oral	DEXTROAMPHETAMINE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
60.7 ng × h/mL	70 mg 1 times / day multiple, oral		LISDEXAMFETAMINE plasma	Homo sapiens
431 ng × h/mL	10 mg single, oral		DEXTROAMPHETAMINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
12 h	70 mg 1 times / day multiple, oral	LISDEXAMFETAMINE plasma	Homo sapiens
12.1 h	10 mg single, oral	DEXTROAMPHETAMINE plasma	Homo sapiens
12 h	15 mg single, oral	DEXTROAMPHETAMINE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
70 mg 1 times / day multiple, oral Recommended	unhealthy, 13 - 17	Disc. AE: Irritability, Decreased appetite...
1200 mg single, oral Overdose	healthy, 17	Disc. AE: Delirium, Tachycardia...
70 mg 1 times / day multiple, oral Recommended	unhealthy, 18 - 55	Disc. AE: Insomnia, Tachycardia...
70 mg 1 times / day multiple, oral Recommended	unhealthy, 6 - 12	Disc. AE: Ventricular hypertrophy, Tic...
30 mg 1 times / day steady, oral	unhealthy, adolescents	Other AEs: Decreased appetite, Insomnia...

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AEs

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AE	Significance	Dose	Population
Decreased appetite	0.86% Disc. AE	70 mg 1 times / day multiple, oral Recommended	unhealthy, 13 - 17
Insomnia	0.86% Disc. AE	70 mg 1 times / day multiple, oral Recommended	unhealthy, 13 - 17
Irritability	1.3% Disc. AE	70 mg 1 times / day multiple, oral Recommended	unhealthy, 13 - 17
Hypertension	Disc. AE	1200 mg single, oral Overdose	healthy, 17
Tachycardia	Disc. AE	1200 mg single, oral Overdose	healthy, 17

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1,587	inhibitor 1,767	substrate 1,217 inhibitor 1,852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2A6 707 CYP2B6 810 CYP2C19 1,478	CYP 270

Drug as perpetrator

Show entries

Target	Modality	Activity
CYP2D6 1,891	inhibitor 3,277	likely
CYP2C19 1,553	inhibitor 3,277	no [Inhibition 87.3 uM]
CYP2C9 1,819	inhibitor 3,277	no [Inhibition 89 uM]
CYP2D6 1,891	inhibitor 3,277	no [Inhibition 90 uM]
CYP2B6 1,001	inhibitor 3,277	no [Inhibition 90.8 uM]

Showing 1 to 5 of 8 entries

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Drug as victim

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Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1,217	substrate 3,367	likely		likely (co-administration study)
CYP 270	substrate 3,367	no

Showing 1 to 2 of 2 entries

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Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00E9T8
Alfa Chemistry	ACM608137333
Angene	AGN-PC-0WH4QC
Cayman Chemical	18050
ChemMol	44007218	http://www.chemmol.com/chemmol/44007218.html

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PubMed

Show entries

Title	Date	PubMed
Neuronal degeneration in the limbic system of weanling rats exposed to saline, hyperthermia or d-amphetamine.	2000 Dec 8	11102570
Dopaminergic mRNA expression in the intact substantia nigra of unilaterally 6-OHDA-lesioned and grafted rats: an in situ hybridization study.	2001	11314769
Stimulation of metabotropic but not ionotropic glutamatergic receptors in the nucleus accumbens is required for the D-amphetamine-induced release of functional dopamine.	2001	11246154
Effects of systemic injections of dopaminergic agents on the habituation of rats submitted to an open field test.	2001	11174051
The purinergic P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid prevents both the acute locomotor effects of amphetamine and the behavioural sensitization caused by repeated amphetamine injections in rats.	2001	11166110

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Patents

Sample Use Guides

In Vivo Use Guide

Usual dose is 5 to 60 mg per day in divided doses, depending on the individual patient response. Narcolepsy seldom occurs in children under 12 years of age; however, when it does, DEXEDRINE may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until an optimal response is obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until an optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. SPANSULE capsules may be used for once-a-day dosage wherever appropriate.

Route of Administration: Oral

In Vitro Use Guide

Unknown