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Identification
Name Atomoxetine
Accession Number DB00289 (APRD00614)
Type small molecule
Groups approved
Description

Atomoxetine is the first non-stimulant drug approved for the treatment of attention-deficit hyperactivity disorder (ADHD). It is sold in the form of the hydrochloride salt of atomoxetine. This chemical is manufactured and marketed under the brand name Strattera; by Eli Lilly and Company and as a generic Attentin by Torrent Pharmaceuticals. There is currently no generic available within the United States due to patent restrictions. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Tomoxetina [Spanish]
Tomoxetine
Tomoxetine [INN]
Tomoxetinum [Latin]
Salts Not Available
Brand names
Name Company
Strattera
Brand mixtures Not Available
Categories
  • Antidepressants
  • Adrenergic Uptake Inhibitors
  • Central Nervous System Agents
CAS number 82248-59-7
Weight Average: 255.3547
Monoisotopic: 255.162314299
Chemical Formula C17H21NO
InChI Key InChIKey=VHGCDTVCOLNTBX-QGZVFWFLSA-N
InChI
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
Plain Text
IUPAC Name
methyl[(3R)-3-(2-methylphenoxy)-3-phenylpropyl]amine
SMILES
CNCC[C@@H](OC1=CC=CC=C1C)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpropylamines
Substructures
  • Benzyl Alcohols and Derivatives
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aromatic compounds
  • Anisoles
  • Phenylpropylamines
  • Phenyl Esters
Pharmacology
Indication For the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) alone or in combination with behavioral treatment, as an adjunct to psychological, educational, social, and other remedial measures.
Pharmacodynamics Atomoxetine is the first non-stimulant drug approved for the treatment of attention-deficit hyperactivity disorder (ADHD). Atomoxetine is classified as a norepinephrine reuptake inhibitor, and is approved for use in children, adolescents, and adults. However, its efficacy has not been studied in children under six years old. Its advantage over stimulants for the treatment of ADHD is that it has less abuse potential than stimulants, is not scheduled as a controlled substance and has proven in clinical trials to offer 24 hour coverage of symptoms associated with ADHD in adults and children.
Mechanism of action 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, as determined through in-vitro studies. Atomoxetine appears to have minimal affinity for other noradrenergic receptors or for other neurotransmitter transporters or receptors.
Absorption Atomoxetine is rapidly absorbed after oral administration, with absolute bioavailability of about 63% in EMs and 94% in PMs. Drugs that elevate gastric pH (magnesium hydroxide/aluminum hydroxide, omeprazole) have no effect on atomoxetine bioavailability. Absorption is minimally affected by food.
Volume of distribution
  • 0.85 L/kg
Protein binding At therapeutic concentrations, 98% of atomoxetine in plasma is bound to protein, primarily albumin.
Metabolism Atomoxetine is primarily metabolized by the CYP2D6 pathway to 4-hydroxyatomoxetine. 4-Hydroxyatomoxetine is equipotent to atomoxetine as an inhibitor of the norepinephrine transporter but circulates in plasma at much lower concentrations (1% of atomoxetine concentration in EMs and 0.1% of atomoxetine concentration in PMs).
Route of elimination Not Available
Half life 5 hours
Clearance
  • 0.35 L/hr/kg [after oral administration in adult extensive metabolizers]
  • 0.03 L/hr/kg [administration of atomoxetine to poor metabolizers]
Toxicity The most commonly reported symptoms accompanying acute and chronic overdoses are somnolence, agitation, hyperactivity, abnormal behavior, and gastrointestinal symptoms.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Capsule Oral 10 mg
Capsule Oral 18 mg
Capsule Oral 25 mg
Capsule Oral 40 mg
Capsule Oral 60 mg
Prices
Unit description Cost Unit
Strattera 80 mg capsule 6.94 USD capsule
Strattera 100 mg capsule 6.83 USD capsule
Strattera 40 mg capsule 6.43 USD capsule
Strattera 60 mg capsule 6.43 USD capsule
Strattera 18 mg capsule 6.03 USD capsule
Strattera 25 mg capsule 5.85 USD capsule
Strattera 10 mg capsule 5.84 USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 5658590 1997-05-26 2017-05-26
Canada 2209735 2002-10-01 2016-01-04
Properties
State solid
Experimental Properties
Property Value Source
water solubility 27.8 mg/mL Not Available
logP 3.9 Not Available
Predicted Properties
Property Value Source
water solubility 3.90e-03 g/l ALOGPS
logP 3.95 ALOGPS
logP 3.81 ChemAxon
logS -4.8 ALOGPS
pKa (strongest basic) 9.8 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 21.26 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 79.44 ChemAxon
polarizability 29.79 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Spencer TJ, Faraone SV, Michelson D, Adler LA, Reimherr FW, Glatt SJ, Biederman J: Atomoxetine and adult attention-deficit/hyperactivity disorder: the effects of comorbidity. J Clin Psychiatry. 2006 Mar;67(3):415-20. Pubmed
  2. Pilhatsch MK, Burghardt R, Wandinger KP, Bauer M, Adli M: Augmentation with atomoxetine in treatment-resistant depression with psychotic features. A case report. Pharmacopsychiatry. 2006 Mar;39(2):79-80. Pubmed
  3. Carpenter LL, Milosavljevic N, Schecter JM, Tyrka AR, Price LH: Augmentation with open-label atomoxetine for partial or nonresponse to antidepressants. J Clin Psychiatry. 2005 Oct;66(10):1234-8. Pubmed
  4. Kratochvil CJ, Newcorn JH, Arnold LE, Duesenberg D, Emslie GJ, Quintana H, Sarkis EH, Wagner KD, Gao H, Michelson D, Biederman J: Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms. J Am Acad Child Adolesc Psychiatry. 2005 Sep;44(9):915-24. Pubmed
  5. McElroy SL, Guerdjikova A, Kotwal R, Welge JA, Nelson EB, Lake KA, Keck PE Jr, Hudson JI: Atomoxetine in the treatment of binge-eating disorder: a randomized placebo-controlled trial. J Clin Psychiatry. 2007 Mar;68(3):390-8. Pubmed
  6. Purper-Ouakil D, Fourneret P, Wohl M, Reneric JP: [Atomoxetine: a new treatment for Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents] Encephale. 2005 May-Jun;31(3):337-48. Pubmed# Simpson D, Plosker GL: Atomoxetine: a review of its use in adults with attention deficit hyperactivity disorder. Drugs. 2004;64(2):205-22. Pubmed
  7. Montoya A, Hervas A, Cardo E, Artigas J, Mardomingo MJ, Alda JA, Gastaminza X, Garcia-Polavieja MJ, Gilaberte I, Escobar R: Evaluation of atomoxetine for first-line treatment of newly diagnosed, treatment-naive children and adolescents with attention deficit/hyperactivity disorder. Curr Med Res Opin. 2009 Nov;25(11):2745-54. Pubmed
  8. Gaillez C, Sorbara F, Perrin E: [Atomoxetine (Strattera), an alternative in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children] Encephale. 2007 Sep;33(4 Pt 1):621-8. Pubmed
External Links
Resource Link
KEGG Drug D02574 Link_out
PubChem Compound 54841 Link_out
PubChem Substance 46506160 Link_out
ChemSpider 49516 Link_out
BindingDB 50133749 Link_out
ChEBI 127342 Link_out
ChEMBL 127342 Link_out
Therapeutic Targets Database DAP000721 Link_out
PharmGKB PA134688071 Link_out
Drug Product Database 2262800 Link_out
RxList http://www.rxlist.com/cgi/generic3/strattera.htm Link_out
Drugs.com http://www.drugs.com/cdi/atomoxetine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Atomoxetine Link_out
ATC Codes
  • N06BA09
AHFS Codes
  • 28:92.00
PDB Entries Not Available
FDA label show (72.8 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Amiodarone The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Chloroquine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Cocaine CYP2D6 Inhibitors (Strong) such as cocaine may increase the serum concentration of atomoxetine. Initiate atomoxetine at a reduced dose (patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. The dose should only be increased to usual doses if symptoms fail to improve after 4 weeks. Patients established on atomoxetine therapy may require dosage reductions and should be monitored for increased levels/adverse effects with initiation/dose increase of a strong CYP2D6 inhibitor.
Diphenhydramine Diphenhydramine, a moderate CYP2D6 inhibitor, may increase the therapeutic and adverse effects of atomoxetine by decreasing its metabolism.
Fluoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Fluphenazine Risk of additive CNS depressant effects. Monitor for increased CNS depression during concomitant therapy.
Haloperidol The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Isocarboxazid Possible severe adverse reaction with this combination
Lomustine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Mibefradil The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Paroxetine The CYP2D6 inhibitor, paroxetine, may increase the effect and toxicity of atomoxetine.
Perphenazine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Phenelzine Possible severe adverse reaction with this combination
Propoxyphene The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Quinacrine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Quinidine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Quinidine barbiturate The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Quinine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Rasagiline Possible severe adverse reaction with this combination
Ritonavir The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Terbinafine Terbinafine, a CYP2D6 inhibitor, may reduce the metabolism and clearance of Atomoxetine. Consider alternate therapy or monitor for therapeutic/adverse effects of Atomoxetine if Terbinafine is initiated, discontinued or dose changed.
Thioridazine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Tranylcypromine The MAO inhibitor, Tranylcypromine, may increase the central neurotoxic effects of the Atomoxetine. These agents should not be administered within 14 days of each other.
Triprolidine The CNS depressants, Triprolidine and Atomoxetine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Vinorelbine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Yohimbine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Food Interactions
  • In the presence of food, the absorption rate is reduced, without the quantity absorbed being affected.
  • Take without regard to meals.
Targets

1. Sodium-dependent noradrenaline transporter

Pharmacological action: yes

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P23975 Link_out
Gene: SLC6A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Biederman J, Heiligenstein JH, Faries DE, Galil N, Dittmann R, Emslie GJ, Kratochvil CJ, Laws HF, Schuh KJ: Efficacy of atomoxetine versus placebo in school-age girls with attention-deficit/hyperactivity disorder. Pediatrics. 2002 Dec;110(6):e75. Pubmed
  2. Spencer T, Heiligenstein JH, Biederman J, Faries DE, Kratochvil CJ, Conners CK, Potter WZ: Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2002 Dec;63(12):1140-7. Pubmed
  3. Michelson D, Adler L, Spencer T, Reimherr FW, West SA, Allen AJ, Kelsey D, Wernicke J, Dietrich A, Milton D: Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Biol Psychiatry. 2003 Jan 15;53(2):112-20. Pubmed
  4. Wernicke JF, Faries D, Girod D, Brown J, Gao H, Kelsey D, Quintana H, Lipetz R, Michelson D, Heiligenstein J: Cardiovascular effects of atomoxetine in children, adolescents, and adults. Drug Saf. 2003;26(10):729-40. Pubmed
  5. Wernicke JF, Adler L, Spencer T, West SA, Allen AJ, Heiligenstein J, Milton D, Ruff D, Brown WJ, Kelsey D, Michelson D: Changes in symptoms and adverse events after discontinuation of atomoxetine in children and adults with attention deficit/hyperactivity disorder: a prospective, placebo-controlled assessment. J Clin Psychopharmacol. 2004 Feb;24(1):30-5. Pubmed
  6. Garnock-Jones KP, Keating GM: Atomoxetine: a review of its use in attention-deficit hyperactivity disorder in children and adolescents. Paediatr Drugs. 2009;11(3):203-26. Pubmed
  7. Kaplan S, Heiligenstein J, West S, Busner J, Harder D, Dittmann R, Casat C, Wernicke JF: Efficacy and safety of atomoxetine in childhood attention-deficit/hyperactivity disorder with comorbid oppositional defiant disorder. J Atten Disord. 2004 Oct;8(2):45-52. Pubmed
  8. Purper-Ouakil D, Fourneret P, Wohl M, Reneric JP: [Atomoxetine: a new treatment for Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents] Encephale. 2005 May-Jun;31(3):337-48. Pubmed
  9. Gaillez C, Sorbara F, Perrin E: [Atomoxetine (Strattera), an alternative in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children] Encephale. 2007 Sep;33(4 Pt 1):621-8. Pubmed
  10. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed

2. Sodium-dependent serotonin transporter

Pharmacological action: unknown

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P31645 Link_out
Gene: SLC6A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Purper-Ouakil D, Fourneret P, Wohl M, Reneric JP: [Atomoxetine: a new treatment for Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents] Encephale. 2005 May-Jun;31(3):337-48. Pubmed
  2. Garnock-Jones KP, Keating GM: Atomoxetine: a review of its use in attention-deficit hyperactivity disorder in children and adolescents. Paediatr Drugs. 2009;11(3):203-26. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19