ATOMOXETINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H21NO
Molecular Weight	255.3547
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNCC[C@@H](OC1=CC=CC=C1C)C2=CC=CC=C2

InChI

InChIKey=VHGCDTVCOLNTBX-QGZVFWFLSA-N

InChI=1S/C17H21NO/c1-14-8-6-7-11-16(14)19-17(12-13-18-2)15-9-4-3-5-10-15/h3-11,17-18H,12-13H2,1-2H3/t17-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21411_strattera_lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/pro/atomoxetine.html

Atomoxetine is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder. The precise mechanism by which atomoxetine produces its therapeutic effects in Attention-Deficit/Hyperactivity Disorder (ADHD) is unknown, but is thought to be related to selective inhibition of the pre-synaptic norepinephrine transporter. Most common adverse reactions are: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence, constipation, dry mouth, dizziness, erectile dysfunction, and urinary hesitation. Atomoxetine is a substrate for CYP2D6 and hence concurrent treatment with CYP2D6 inhibitors such as bupropion (Wellbutrin) or fluoxetine (Prozac) is not recommended, as this can lead to significant elevations of plasma atomoxetine levels.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Norepinephrine transporter 197 Target ID: CHEMBL222 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21411_strattera_lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/12431845 \| https://www.ncbi.nlm.nih.gov/pubmed/23933039	Inhibitor 8504	5.0 nM [Ki]
Serotonin transporter 183 Target ID: CHEMBL228 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12431845 \| https://www.ncbi.nlm.nih.gov/pubmed/23933039	Inhibitor 8504	77.0 nM [Ki]
Dopamine transporter 183 Target ID: CHEMBL238 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12431845	Inhibitor 8504	1451.0 nM [Ki]
Glutamate receptor ionotropic, NMDA 2A 3 Target ID: Q00959 Gene ID: 24409.0 Gene Symbol: Grin2a Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20423340	Antagonist 2849	1.58 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Attention deficit hyperactivity disorder 70 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21411_strattera_lbl.pdf	Primary		Approved 8583	STRATTERA Approved Use Attention-Deficit/Hyperactivity Disorder (ADHD) STRATTERA is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). The efficacy of STRATTERA Capsules was established in seven clinical trials in outpatients with ADHD: four 6 to 9-week trials in pediatric patients (ages 6 to 18), two 10-week trial in adults, and one maintenance trial in pediatrics (ages 6 to 15) [see Clinical Studies (14) Launch Date 2002

C_max

Value	Dose	Co-administered	Analyte	Population
414.82 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23812961	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		ATOMOXETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
2693.29 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23812961	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		ATOMOXETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.64 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23812961	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		ATOMOXETINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021411s035lbl.pdf			ATOMOXETINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087 substrate 1946	inhibitor 2438 inducer 440 substrate 1193	substrate 1388 inhibitor 2507 inducer 109	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153	P-gp 2052 CYP2C19 1119 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2E1 729	CYP1A2 832

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 11, 30	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 11, 30	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 11, 30	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 11, 30	no
CYP2D6 2546	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 11, 30	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 11, 30	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 11, 28, 30	no	no (co-administration study) Comment: coadministration with desipramine did not alter the PK of desipramine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 11, 28, 30
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 11, 28, 30	no	no (co-administration study) Comment: coadministration with midazolam increased AUC by 15% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 11, 28, 30

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 8, 11, 22	major	yes (co-administration study) Comment: coadministration with paroxetine or fluoxetine increased atomoxetine steady-state plasma concentrations Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 8, 11, 22
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17963743/	unlikely
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 22.0	weak
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 22.0	weak
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 22.0	weak
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 22.0	weak
CYP2E1 729	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 22.0	weak
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 22.0	weak
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_biopharmr_P1.pdf Page: 22.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-411_Strattera_pharmr_P1.pdf Page: 15.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:127342	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:127342
ChemicalBook	CB3378328	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3378328
eMolecules	1883572	https://www.emolecules.com/cgi-bin/more?vid=1883572
MolPort	MolPort-002-052-062	https://www.molport.com/shop/molecule-link/MolPort-002-052-062
ZINC	ZINC000001842633	http://zinc15.docking.org/substances/ZINC000001842633

PubMed

Title	Date	PubMed
Atomoxetine hydrochloride for the treatment of attention-deficit/hyperactivity disorder.	2003 Dec	14749146
Non-stimulant medications in the treatment of ADHD.	2004	15322961
Involvement of norepinephrine in the control of activity and attentive processes in animal models of attention deficit hyperactivity disorder.	2004	15303310
Spotlight on atomoxetine in adults with attention-deficit hyperactivity disorder.	2004	15089111
Impact of ADHD and its treatment on substance abuse in adults.	2004	15046534
ADHD treatment across the life cycle.	2004	15046532
Atomoxetine: a review of its use in adults with attention deficit hyperactivity disorder.	2004	14717619
Seizures and prolonged QTc with atomoxetine overdose.	2004 Apr	15056530
A prospective, multicenter, open-label assessment of atomoxetine in non-North American children and adolescents with ADHD.	2004 Aug	15365896
Role of presynaptic alpha2-adrenoceptors in antidepressant action: recent findings from microdialysis studies.	2004 Aug	15363606
Atomoxetine, a novel treatment for attention-deficit-hyperactivity disorder.	2004 Aug	15338851
Improvement in health-related quality of life in children with ADHD: an analysis of placebo controlled studies of atomoxetine.	2004 Aug	15308927
Atomoxetine (Strattera) revisited.	2004 Aug 16	15314585
Synthesis and biological evaluation of the major metabolite of atomoxetine: elucidation of a partial kappa-opioid agonist effect.	2004 Aug 2	15225731
[Tourette syndrome: an analysis of its comorbidity and specific treatment].	2004 Feb	15011166
[New therapeutic options in the treatment of attention deficit/hyperactivity disorder].	2004 Feb	15011165
New drugs 04, part 1.	2004 Feb	14758333
Atomoxetine treatment of attention-deficit/hyperactivity disorder.	2004 Jan	14742801
Gateways to clinical trials.	2004 Jan-Feb	14988742
The use of atomoxetine adjunctively in fibromyalgia syndrome.	2004 Jul	15362262
New options in the pharmacological management of attention-deficit/hyperactivity disorder.	2004 Jul	15352538
Attention-deficit/hyperactivity disorder: medication treatment-dosing and duration of action.	2004 Jul	15352536
Once-daily atomoxetine treatment for children with attention-deficit/hyperactivity disorder, including an assessment of evening and morning behavior: a double-blind, placebo-controlled trial.	2004 Jul	15231966
Relapse prevention in pediatric patients with ADHD treated with atomoxetine: a randomized, double-blind, placebo-controlled study.	2004 Jul	15213591
The link between health-related quality of life and clinical symptoms among children with attention-deficit hyperactivity disorder.	2004 Jun	15194901
Acute oxcarbazepine and atomoxetine overdose with quetiapine.	2004 Jun	15171487
Pharmacological management of attention-deficit hyperactivity disorder.	2004 Jun	15163276
Nonstimulant treatment of adult attention-deficit/hyperactivity disorder.	2004 Jun	15064003
Driving impairments in teens and adults with attention-deficit/hyperactivity disorder.	2004 Jun	15063996
Evidence-based pharmacotherapy for attention-deficit hyperactivity disorder.	2004 Mar	14733627
New drugs of 2003.	2004 Mar-Apr	15098851
[Attention-deficit/hyperactivity disorder (ADHS) in adulthood].	2004 Mar-Apr	15037976
Atomoxetine--treatment of attention deficit hyperactivity disorder: beyond stimulants.	2004 May	15319800
Atomoxetine hydrochloride.	2004 May	15152632
Potential noradrenergic targets for cognitive enhancement in schizophrenia.	2004 May	15115947
Adrenergic alpha 2C receptor genomic organization: association study in adult ADHD.	2004 May 15	15108182
New drugs for the treatment of attention-deficit/hyperactivity disorder.	2004 Nov	15571486
Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication.	2004 Nov	15554766
Atomoxetine: the first nonstimulant for the management of attention-deficit/hyperactivity disorder.	2004 Nov 15	15581262
A lifetime of distractions. ADHD is no longer just a children's disease. Many adults are being diagnosed and treated for the condition.	2004 Oct	15496372
[Atomoxetine for the treatment of attention-deficit/hyperactivity disorder].	2004 Oct	15472782
Mania induction associated with atomoxetine.	2004 Oct	15349024
Management of hyperactivity and other acting-out problems in patients with autism spectrum disorder.	2004 Sep	15575418
Gateways to clinical trials.	2004 Sep	15538546
Aggression, mania, and hypomania induction associated with atomoxetine.	2004 Sep	15342872
Atomoxetine and nonresponders to stimulants.	2004 Sep	15337674
Atomoxetine and tics in ADHD.	2004 Sep	15322408
Evaluation of the reinforcing effects of atomoxetine in monkeys: comparison to methylphenidate and desipramine.	2004 Sep 6	15283948
Atomoxetine and stimulants in combination for treatment of attention deficit hyperactivity disorder: four case reports.	2004 Spring	15142400
Evaluation of the reinforcing effects of monoamine reuptake inhibitors under a concurrent schedule of food and i.v. drug delivery in rhesus monkeys.	2005 Apr	15526000

Patents

Sample Use Guides

In Vivo Use Guide

Atomoxetine should be initiated at a total daily dose of approximately 0.5 mg/kg and increased after a minimum of 3 days to a target total daily dose of approximately 1.2 mg/kg administered either as a single daily dose in the morning or as evenly divided doses in the morning and late afternoon/early evening. No additional benefit has been demonstrated for doses higher than 1.2 mg/kg/day.

Route of Administration: Oral

In Vitro Use Guide

Electrophysiological recordings was performed with the extracellular standard solution at different membrane potentials ranging from -80 mV to +40 mV while the concentration of the agonists (100 uM NMDA/10 uM glycine) and the antagonist (25 uM atomoxetine) were kept constant. The inhibitory effect was clearly voltage-dependent, so that the inhibition was attenuated by depolarization.

Name

Type

Language

ATOMOXETINE

Official Name

English

ATOMOXETINE [HSDB]

Preferred Name

English

AD-109 COMPONENT ATOMOXETINE

Common Name

English

AD313 COMPONENT ATOMOXETINE

Code

English

atomoxetine [INN]

Common Name

English

Atomoxetine [WHO-DD]

Common Name

English

AD109 COMPONENT ATOMOXETINE

Common Name

English

ATOMOXETINE [VANDF]

Common Name

English

AD-313 COMPONENT ATOMOXETINE

Code

English

ATOMOXETINE [MI]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N06BA09