title: A review of the abuse potential assessment of atomoxetine: a nonstimulant medication for attention-deficit/hyperactivity disorder.
abstract: BACKGROUND
  Treatment of attention-deficit/hyperactivity disorder (ADHD) has for many years relied on psychostimulants, particularly various formulations of amphetamines and methylphenidate. These are central nervous system stimulants and are scheduled because of their abuse potential. Atomoxetine (atomoxetine hydrochloride; Strattera®) was approved in 2002 for treatment of ADHD, and was the first nonstimulant medication approved for this disorder. It was classified as an unscheduled medication indicating a low potential for abuse. However, the abuse potential of atomoxetine has not been reviewed.
  
  
  OBJECTIVE
  In this article, we review the evidence regarding abuse potential of atomoxetine, a selective inhibitor of the presynaptic norepinephrine transporter, which is unscheduled/unrestricted in all countries where it is approved.
  
  
  METHODS
  Results from receptor binding, in vitro electrophysiology, in vivo microdialysis, preclinical behavioral, and human laboratory studies have been reviewed.
  
  
  RESULTS
  Atomoxetine has no appreciable affinity for, or action at, central receptors through which drugs of abuse typically act, i.e., dopamine transporters, GABA(A) receptors, and opioid μ receptors. In behavioral experiments in rodents, atomoxetine does not increase locomotor activity, and in drug discrimination studies, its profile is similar to that of drugs without abuse potential. Atomoxetine does not serve as a reinforcer in monkey self-administration studies, and human laboratory studies suggest that atomoxetine does not induce subjective effects indicative of abuse.
  
  
  CONCLUSIONS
  Neurochemical, preclinical, and early clinical studies predicted and supported a lack of abuse potential of atomoxetine, which is consistent with the clinical trial and postmarketing spontaneous event data in the past 10 years.
authors: Eli Lilly and Company, Indianapolis, IN 46285, USA. upadhyayahp@lilly.com
authors: Himanshu P
authors: HP
authors: Upadhyaya
authors: Durisala
authors: D
authors: Desaiah
authors: Kory J
authors: KJ
authors: Schuh
authors: Frank P
authors: FP
authors: Bymaster
authors: Mary J
authors: MJ
authors: Kallman
authors: David O
authors: DO
authors: Clarke
authors: Todd M
authors: TM
authors: Durell
authors: Paula T
authors: PT
authors: Trzepacz
authors: David O
authors: DO
authors: Calligaro
authors: Eric S
authors: ES
authors: Nisenbaum
authors: Paul J
authors: PJ
authors: Emmerson
authors: Leslie M
authors: LM
authors: Schuh
authors: Warren K
authors: WK
authors: Bickel
authors: Albert J
authors: AJ
authors: Allen
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D016739:Behavior, Addictive / Q000378:metabolism; D058999:Drug-Seeking Behavior / Q000187:drug effects; D006801:Humans; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D011437:Propylamines / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D011485:Protein Binding / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D019966:Substance-Related Disorders / Q000503:physiopathology*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011437:Propylamines; D017981:Receptors, Neurotransmitter; D000069445:Atomoxetine Hydrochloride
references: Int J Clin Pract. 2007 Oct;61(10):1730-8
references: 17877659
references: J Clin Psychiatry. 2007;68 Suppl 11:23-30
references: 18307378
references: Science. 1987 Sep 4;237(4819):1219-23
references: 2820058
references: J Pharmacol Exp Ther. 2006 Oct;319(1):237-46
references: 16835371
references: Drug Alcohol Depend. 2004 Sep 6;75(3):271-6
references: 15283948
references: Drugs. 2004;64(2):205-22
references: 14717619
references: J Neurosci. 2000 Aug 1;20(15):5575-80
references: 10908593
references: Drug Alcohol Depend. 2008 May 1;95(1-2):140-6
references: 18328639
references: Prog Brain Res. 1990;86:287-94
references: 2128418
references: J Pharmacol Exp Ther. 1975 May;193(2):676-88
references: 1142112
references: Psychopharmacology (Berl). 1995 Aug;120(3):303-10
references: 8524978
references: Am J Psychiatry. 2003 Nov;160(11):1909-18
references: 14594733
references: Psychopharmacology (Berl). 2011 Jul;216(2):153-71
references: 21360099
references: J Pharmacol Exp Ther. 2009 Jul;330(1):236-48
references: 19357320
references: Mol Psychiatry. 2009 Feb;14(2):123-42
references: 18698321
references: J Pharmacol Exp Ther. 1995 Oct;275(1):53-62
references: 7562595
references: Mol Pharmacol. 1994 Jan;45(1):125-35
references: 8302271
references: Arch Intern Med. 1991 Apr;151(4):781-3
references: 1849397
references: Drug Alcohol Depend. 2002 Jul 1;67(2):149-56
references: 12095664
references: J Nerv Ment Dis. 1997 Aug;185(8):475-82
references: 9284860
references: Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58
references: 9537821
references: Neuropsychopharmacology. 2002 Nov;27(5):699-711
references: 12431845
references: World Psychiatry. 2003 Jun;2(2):104-13
references: 16946911
references: J Abnorm Psychol. 2003 Aug;112(3):497-507
references: 12943028
references: J Pharmacol Exp Ther. 1998 Jun;285(3):1163-74
references: 9618419
references: CNS Drugs. 2010 Jan;24(1):85-8
references: 20030421
references: J Neurophysiol. 1997 Nov;78(5):2280-6
references: 9356381
references: J Clin Psychopharmacol. 2004 Feb;24(1):30-5
references: 14709944
references: J Neurochem. 2010 Jul;114(1):259-70
references: 20403082
references: Drug Alcohol Depend. 2008 Jul 1;96(1-2):145-54
references: 18403134
references: J Abnorm Psychol. 2002 May;111(2):279-89
references: 12003449
references: J Neurosci. 2002 Oct 1;22(19):8705-10
references: 12351745
references: J Child Adolesc Psychopharmacol. 2005 Oct;15(5):799-809
references: 16262596
references: J Pharmacol Exp Ther. 1991 Dec;259(3):1088-93
references: 1762063
references: J Am Acad Child Adolesc Psychiatry. 1997 Jan;36(1):21-9
references: 9000777
references: J Pharmacol Exp Ther. 1994 Nov;271(2):1058-66
references: 7965768
references: Expert Opin Drug Discov. 2011 Feb;6(2):109-127
references: 21532928
references: Am J Psychiatry. 1998 May;155(5):693-5
references: 9585725
references: J Pharmacol Exp Ther. 1989 Oct;251(1):150-5
references: 2529365
references: Child Adolesc Psychiatr Clin N Am. 2000 Jul;9(3):481-98
references: 10944652
references: Am J Psychiatry. 1998 Oct;155(10):1325-31
references: 9766762
references: J Neurochem. 1997 May;68(5):2032-7
references: 9109529
references: Brain Res. 2002 May 17;936(1-2):58-67
references: 11988230
references: Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12304-8
references: 8618890
references: Brain Res Dev Brain Res. 2005 Apr 21;156(1):1-12
references: 15862622
references: Am J Addict. 2010 Nov-Dec;19(6):569-77
references: 20958854
references: Pharmacol Biochem Behav. 2010 Jun;95(4):449-56
references: 20346966
references: Nature. 1997 Apr 24;386(6627):827-30
references: 9126740
references: J Am Acad Child Adolesc Psychiatry. 1998 Dec;37(12):1242-3
references: 9847492
references: Br J Pharmacol. 2007 Mar;150(6):711-9
references: 17293887
references: J Am Acad Child Adolesc Psychiatry. 2008 Jan;47(1):21-31
references: 18174822
references: Ann N Y Acad Sci. 1992 Jun 28;654:171-91
references: 1632582
references: Curr Med Res Opin. 2011 Dec;27(12):2309-20
references: 22029549
references: Biol Psychiatry. 2003 Jan 15;53(2):112-20
references: 12547466
references: Psychopharmacology (Berl). 1999 Nov;147(1):96-103
references: 10591874
references: J Forensic Sci. 1999 Jan;44(1):220-1
references: 9987890
references: Life Sci. 1996;58(12):231-9
references: 8786705
references: Neuropharmacology. 1996 Jan;35(1):63-70
references: 8684598
references: J Neurosci Methods. 1989 Sep;29(3):261-5
references: 2507830
references: Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14128-33
references: 8943072
references: Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3495-500
references: 15728379
references: Am J Addict. 2007;16 Suppl 1:35-42; quiz 43-4
references: 17453605
references: J Pharmacol Exp Ther. 1994 Sep;270(3):1041-8
references: 7932151
references: Am J Psychiatry. 2002 Nov;159(11):1896-901
references: 12411225
references: J Neurosci. 2001 Jan 15;21(2):RC121
references: 11160455
references: J Pharmacol Exp Ther. 1993 Oct;267(1):1-8
references: 8229735
references: Psychopharmacologia. 1971;22(3):271-81
references: 4399836
references: Neuropsychopharmacology. 2005 Apr;30(4):758-64
references: 15526000
references: J Clin Psychiatry. 2002 Dec;63(12):1140-7
references: 12523874
references: J Pharmacol Exp Ther. 2007 Jun;321(3):1135-43
references: 17351103
references: Dis Mon. 2007 Feb;53(2):70-131
references: 17386306
references: Exp Clin Psychopharmacol. 2006 May;14(2):136-47
references: 16756417
references: J Pharmacol Exp Ther. 1990 Jul;254(1):312-7
references: 2195158
references: Psychopharmacology (Berl). 2000 Dec;153(1):67-84
references: 11255930
references: Subst Abuse Treat Prev Policy. 2007 Oct 31;2:32
references: 17974020
references: Neuropsychopharmacology. 2005 May;30(5):901-15
references: 15637641
references: Am J Psychiatry. 2006 Apr;163(4):716-23
references: 16585449
references: Neurochem Int. 1992 Mar;20 Suppl:231S-235S
references: 1365432
references: Compr Psychiatry. 1990 Sep-Oct;31(5):416-25
references: 2225800
references: Life Sci. 1992;51(9):631-45
references: 1501510
references: J Clin Psychopharmacol. 2001 Jun;21(3):273-86
references: 11386490