塩酸アトモキセチン

関: atomoxetine

WordNet

a complex consisting of an organic base in association with hydrogen chloride

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/08/03 23:08:26」(JST)

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Atomoxetine (brand name: Strattera) is a norepinephrine (noradrenaline) reuptake inhibitor which is approved for the treatment of attention deficit hyperactivity disorder (ADHD).^[4] As of 2017 it is available as a generic medication in the United States.^[5]

Medical use

Attention deficit hyperactivity disorder

Atomoxetine is approved for use in children, adolescents, and adults.^[4] However, its efficacy has not been studied in children under six years old.^[2] Its primary advantage over the standard stimulant treatments for ADHD is that it has little known abuse potential.^[2] While it has been shown to significantly reduce inattentive and hyperactive symptoms, the responses were lower than the response to stimulants. Additionally, 40% of participants who were treated with atomoxetine experienced significant residual ADHD symptoms.^[6]

The initial therapeutic effects of atomoxetine usually take 2–4 weeks to become apparent.^[1] A further 2–4 weeks may be required for the full therapeutic effects to be seen.^[7] Its efficacy may be less than that of stimulant medications.^[8]

Unlike α₂ adrenoceptor agonists such as guanfacine and clonidine, atomoxetine's use can be abruptly stopped without significant discontinuation effects being seen.^[2]

Adverse effects

Incidence of adverse effects:^[2]^[3]^[9]^[10]

Very common (>10% incidence) adverse effects include:

Nausea (26%)
Xerostomia (Dry mouth) (20%)
Appetite loss (16%)
Insomnia (15%)
Fatigue (10%)
Headache
Cough

Common (1-10% incidence) adverse effects include:

Constipation (8%)
Dizziness (8%)
Erectile dysfunction (8%)
Somnolence (sleepiness) (8%)
Abdominal pain (7%)
Urinary hesitation (6%)
Tachycardia (high heart rate) (5-10%)
Hypertension (high blood pressure) (5-10%)
Irritability (5%)
Abnormal dreams (4%)
Dyspepsia (4%)
Ejaculation disorder (4%)
Hyperhidrosis (abnormally increased sweating) (4%)
Vomiting (4%)
Hot flashes (3%)
Paraesthesia (sensation of tingling, tickling, etc.) (3%)
Menstrual disorder (3%)
Weight loss (2%)
Depression
Sinus headache
Dermatitis
Mood swings

Uncommon (0.1-1% incidence) adverse effects include:

Suicide-related events
Hostility
Emotional lability
Aggression
Psychosis
Syncope (fainting)
Tremor
Migraine
Hypoaesthesia
Seizure
Palpitations
Sinus tachycardia
QT interval prolongation
Increased blood bilirubin
Allergic reactions

Rare (0.01-0.1% incidence) adverse effects including

Raynaud's phenomenon
Abnormal/increased liver function tests
Jaundice
Hepatitis
Liver injury
Acute liver failure
Urinary retention
Priapism^[11]
Male genital pain

The FDA of the US has issued a black box warning for suicidal behaviour/ideation.^[3] Similar warnings have been issued in Australia.^[2]^[12] Unlike stimulant medications, atomoxetine does not have abuse liability or the potential to cause withdrawal effects on abrupt discontinuation.^[2]

Contraindications

Contraindications include:^[2]

Hypersensitivity to atomoxetine or any of the excipients in the product
Symptomatic cardiovascular disease including:

-moderate to severe hypertension

-atrial fibrillation

-atrial flutter

-ventricular tachycardia

-ventricular fibrillation

-ventricular flutter

-advanced arteriosclerosis

Severe cardiovascular disorders
Phaeochromocytoma
Concomitant treatment with monoamine oxidase inhibitors
Narrow angle glaucoma
Poor metabolizers (due to the metabolism of atomoxetine by CYP2D6)

Interactions

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. CYP2D6 is not very susceptible to enzyme induction.^[13] Other possible drug interactions include:^[2]

Antihypertensive and pressor agents, due to the potential pressor effect of indirect sympathomimetics such as atomoxetine.
Norepinephrine-acting agents such as α₁ adrenoceptor agonists or norepinephrine reuptake inhibitors due to the potential for additive or synergistic pharmacologic effects.
β-adrenoceptor agonists due to the potential for the effects of these drugs to be potentiated by atomoxetine.
Highly plasma protein-bound drugs due to the potential of atomoxetine to displace these drugs from plasma proteins and hence potentiate their adverse effects. Examples include diazepam, paroxetine and phenytoin.

Overdose

Atomoxetine is relatively non-toxic in overdose. Single-drug overdoses involving over 1500 mg of atomoxetine have not resulted in death.^[2] The most common symptoms of overdose include:^[2]

Gastrointestinal symptoms
Somnolence
Dizziness
Tremor
Abnormal behaviour
Hyperactivity
Agitation
Dry mouth
Tachycardia
Hypertension
Mydriasis

Less common symptoms:^[2]

Seizures
QTc interval prolongation

The recommended treatment for atomoxetine overdose includes use of activated charcoal to prevent further absorption of the drug.^[2]

Detection in biological fluids

Atomoxetine may be quantitated in plasma, serum or whole blood in order to distinguish extensive versus poor metabolizers in those receiving the drug therapeutically, to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage.^[14]

Chemistry and composition

Atomoxetine is designated chemically as (−)-N-methyl-3-phenyl-3-(o-tolyloxy)-propylamine hydrochloride, and has a molecular mass of 291.82.^[4] It has a solubility of 27.8 mg/ml in water.^[4] Atomoxetine is a white solid that exists as a granular powder inside the capsule, along with pregelatinized starch and dimethicone.^[4] The capsule shells contain gelatin, sodium lauryl sulfate, FD&C Blue No. 2, yellow iron oxide, titanium dioxide, red iron oxide, edible black ink, and trace amounts of other inactive ingredients.^[4]

Strattera 60-mg capsule back
Strattera 60-mg capsule front with Lilly logo

Pharmacology

Atomoxetine inhibits NET, SERT, and DAT with respective K_i values of 5, 77, and 1451 nM.^[15] In microdialysis studies, it increased NE and DA levels by three-fold in the prefrontal cortex, but did not alter DA levels in the striatum or nucleus accumbens.^[16] Atomoxetine's selective increase in NE and DA are due to a lack of high concentrations of DAT in the prefrontal cortex (where the NET transports DA instead), and the nucleus accumbens's relative paucity of NE neurons.^[17] A PET imaging study of rhesus monkeys found that atomoxetine inhibited the NET and SERT with IC₅₀ values of 31 ng/mL and 99 ng/mL plasma, respectively, and that at clinically relevant doses, atomoxetine would occupy >90% of NET and >85% of SERT.^[18]

Atomoxetine also acts as an NMDA receptor antagonist at clinically relevant doses.^[19] The role of NMDA receptor antagonism in atomoxetine's therapeutic profile remains to be further elucidated, but recent literature has further implicated glutamatergic dysfunction as central in ADHD pathophysiology and etiology.^[20]^[21] 4-Hydroxyatomoxetine, the principle metabolite of atomoxetine, exhibits relatively weak affinity for μ-opioid receptors and κ-opioid receptors. Creighton et al. reported antagonism of μ-opioid receptors and a partial agonist action at κ-opioid receptors.^[22] The clinical significance of these effects are not known. Atomoxetine has been found to inhibit both brain and cardiac G protein-coupled inwardly-rectifying potassium channels, a characteristic it shares with the related drug reboxetine.^[23]

**Binding profile**^[15]^[16]^[22]^[24]
Protein	K_i (nM) for atomoxetine	K_i (nM) for 4-hydroxyatomoxetine
SERT	77	?
NET	5	?
DAT	1451	?
5-HT receptors	>1000	?
Alpha adrenergic receptors	>1000	?
Beta adrenergic receptors	>1000	?
D₁ & D₂	>1000	?
M₁ & M₂	>1000	?
H₁ & H₂	>1000	?
δ₁ opioid receptor	?	300
κ₁ opioid receptor	?	95
μ opioid receptor	?	422
σ₁ receptor	>1000	?

History

Atomoxetine is manufactured, marketed, and sold in the United States as the hydrochloride salt (atomoxetine HCl) under the brand name Strattera by Eli Lilly and Company, the original patent-filing company and current U.S. patent owner. Atomoxetine was initially intended to be developed as an antidepressant, but it was found to be insufficiently efficacious for treating depression. It was, however, found to be effective for ADHD and was approved by the FDA in 2002 for the treatment of ADHD. It is under patent until 2017.^[25] On May 30, 2017 the FDA approved the generic production by four pharmaceutical companies.^[26] On 12 August 2010, Lilly lost a lawsuit that challenged its patent on Strattera, increasing the likelihood of an earlier entry of a generic into the US market.^[27] On 1 September 2010, Sun Pharmaceuticals announced it would begin manufacturing a generic in the United States.^[28] In a 29 July 2011 conference call, however, Sun Pharmaceutical's Chairman stated "Lilly won that litigation on appeal so I think [generic Strattera]’s deferred."^[29]

Brand names

In India, atomoxetine is sold under brand names including Attentrol [Sun Pharma], Axepta, [Intas Pharma] Attera [Icon pharma], Tomoxetin [Torrent Pharma], Atokem [Alkem Pharma], and Attentin [Ranbaxy Pharma].

In Romania, atomoxetine is sold under the brand name Strattera.

In Iran, atomoxetine is sold under brand names including stramox by TeKaJe Co.

Research

There has been some suggestion that atomoxetine might be a helpful adjunct in people with major depression, particularly in cases with concomitant ADHD.^[30]^[31]^[32]

References

^ ^a ^b ^c ^d ^e ^f "atomoxetine (Rx) – Strattera". Medscape Reference. WebMD. Retrieved 10 November 2013.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q "STRATTERA® (atomoxetine hydrochloride)". TGA eBusiness Services. Eli Lilly Australia Pty. Limited. 21 August 2013. Retrieved 10 November 2013.
^ ^a ^b ^c ^d ^e ^f ^g "ATOMOXETINE HYDROCHLORIDE capsule [Mylan Pharmaceuticals Inc.]". DailyMed. Mylan Pharmaceuticals Inc. October 2011. Retrieved 10 November 2013.
^ ^a ^b ^c ^d ^e ^f "STRATTERA^® (atomoxetine hydrochloride) CAPSULES for Oral Use. Full Prescribing Information" (PDF). Indianapolis, USA: Eli Lilly and Company. 20 February 2014. Retrieved 23 May 2014.
^ "Press Announcements - FDA approves first generic Strattera for the treatment of ADHD". www.fda.gov. Retrieved 2 June 2017.
^ Ghuman, Jaswinder K.; Hutchison, Shari L. (2014-11-01). "Atomoxetine is a second-line medication treatment option for ADHD". Evidence Based Mental Health. 17 (4): 108–108. ISSN 1468-960X. PMID 25165169. doi:10.1136/eb-2014-101805.
^ Taylor, D; Paton, C; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 978-0-470-97948-8.
^ Kooij, JJS (2013). Adult ADHD Diagnostic Assessment and Treatment (PDF). Springer London. ISBN 978-1-4471-4137-2. doi:10.1007/978-1-4471-4138-9.
^ "Strattera 10mg, 18mg, 25mg, 40mg, 60mg, 80mg or 100mg hard capsules". electronic Medicines Compendium. 28 May 2013. Retrieved 10 November 2013.
^ "Strattera Product Insert". Retrieved 8 December 2013.
^ "STRATTERA Medication Guide" (PDF). Eli Lilly and Company. 2003. Retrieved 17 December 2013.
^ "Atomoxetine and suicidality in children and adolescents". Australian Prescriber. 36 (5). October 2013. p. 166. Archived from the original on 10 November 2013. Retrieved 10 November 2013.
^ Horn, John R.; Hansten, Philip D. (2008). "Get to Know an Enzyme: CYP2D6". Pharmacy Times. Retrieved 19 February 2015.
^ Baselt, Randall C. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 118–20. ISBN 0-931890-08-X.
^ ^a ^b Roth, BL; Driscol, J (12 January 2011). "PDSP K_i Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 8 November 2013. Retrieved 10 November 2013.
^ ^a ^b Bymaster, FP; Katner, JS; Nelson, DL; Hemrick-Luecke, SK; Threlkeld, PG; Heiligenstein, JH; Morin, SM; Gehlert, DR; Perry, KW (November 2002). "Atomoxetine Increases Extracellular Levels of Norepinephrine and Dopamine in Prefrontal Cortex of Rat: A Potential Mechanism for Efficacy in Attention Deficit/Hyperactivity Disorder" (PDF). Neuropsychopharmacology. 27 (5): 699–711. PMID 12431845. doi:10.1016/S0893-133X(02)00346-9.
^ Stahl, Stephen M. (17 March 2008). "17". Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (3rd ed.). New York: Cambridge University Press. p. 891. ISBN 9780521673761. Retrieved 1 November 2015. Since the prefrontal cortex lacks high concentrations of DAT, DA is inactivated in this part of the brain by NET. Thus, inhibiting NET increases both DA and NE in the prefrontal cortex (Figures 12-36 and 17-21). However, since there are only a few NE neurons and NETs in nucleus accumbens, inhibiting NET does not lead to an increase in either NE or DA there (Figure 17-21). For this reason, in ADHD patients with deficient arousal and weak NE and DA signals in prefrontal cortex, a selective NRI such as atomoxetine increases both NE and DA in prefrontal cortex, enhancing tonic signaling of both, but it increases neither NE nor DA in the nucleus accumbens. Therefore atomoxetine has no abuse potential.
^ Ding, Y.-S.; Naganawa, M.; Gallezot, J.-D.; Nabulsi, N.; Lin, S.-F.; Ropchan, J.; Weinzimmer, D.; McCarthy, T.J.; Carson, R.E.; Huang, Y.; Laruelle, M. (2014). "Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD". NeuroImage. 86: 164–171. ISSN 1053-8119. PMID 23933039. doi:10.1016/j.neuroimage.2013.08.001. The noradrenergic action also exerts an important clinical effect in different antidepressant classes such as desipramine and nortriptyline (tricyclics, prevalent noradrenergic effect), reboxetine and atomoxetine (relatively pure noradrenergic reuptake inhibitor (NRIs)), and dual action antidepressants such as the serotonin noradrenaline reuptake inhibitors (SNRIs), the noradrenergic and dopaminergic reuptake inhibitor (NDRI) bupropion, and other compounds (e.g., mianserin, mirtazapine), which enhance the noradrenergic transmission
^ Ludolph, AG; Udvardi, PT; Schaz, U; Henes, C; Adolph, O; Weigt, HU; Fegert, JM; Boeckers, TM; Föhr, KJ (May 2010). "Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations" (PDF). British Journal of Pharmacology. 160 (2): 283–291. PMC 2874851 . PMID 20423340. doi:10.1111/j.1476-5381.2010.00707.x.
^ Lesch, KP; Merker, S; Reif, A; Novak, M (June 2013). "Dances with black widow spiders: dysregulation of glutamate signalling enters centre stage in ADHD". European Neuropsychopharmacology. 23 (6): 479–491. PMID 22939004. doi:10.1016/j.euroneuro.2012.07.013.
^ "New gene study of ADHD points to defects in brain signaling pathways". Children's Hospital of Philadelphia. 4 December 2011.
^ ^a ^b Creighton, CJ; Ramabadran, K; Ciccone, PE; Liu, J; Orsini, MJ; Reitz, AB (2 August 2004). "Synthesis and biological evaluation of the major metabolite of atomoxetine: elucidation of a partial kappa-opioid agonist effect.". Bioorganic & Medicinal Chemistry Letters. 14 (15): 4083–5. PMID 15225731. doi:10.1016/j.bmcl.2004.05.018.
^ Kobayashi, T; Washiyama, K; Ikeda, K (Jun 2010). "Inhibition of G-protein-activated inwardly rectifying K+ channels by the selective norepinephrine reuptake inhibitors atomoxetine and reboxetine.". Neuropsychopharmacology. 35 (7): 1560–9. PMC 3055469 . PMID 20393461. doi:10.1038/npp.2010.27.
^ Bymaster, FP; Katner, JS; Nelson, DL; Hemrick-Luecke, SK; Threlkeld, PG; Heiligenstein, JH; Morin, SM; Gehlert, DR; Perry, KW (November 2002). "Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder". Neuropsychopharmacology. 27 (5): 699–711. PMID 12431845. doi:10.1016/S0893-133X(02)00346-9.
^ "Patent and Exclusivity Search Results". Electronic Orange Book. US Food and Drug Administration. Retrieved 26 April 2009.
^ [FDA.org/news events/newsroom/press announcements/ucm561096.htm FDA.org/news events/newsroom/press announcements/ucm561096.htm] Check |url= value (help). Missing or empty |title= (help)
^ "Drugmaker Eli Lilly loses patent case over ADHD drug, lowers revenue outlook". Chicago Tribune.
^ "Sun Pharma receives USFDA approval for generic Strattera capsules". International Business Times. Archived from the original on 7 April 2011.
^ "Sun Pharma Q1 2011-12 Earnings Call Transcript 10.00 am, July 29, 2011" (PDF). Archived from the original (PDF) on 29 September 2011.
^ Spencer TJ, Faraone SV, Michelson D, Adler LA, Reimherr FW, Glatt SJ & Biederman J (March 2006). "Atomoxetine and adult attention-deficit/hyperactivity disorder: the effects of comorbidity". The Journal of Clinical Psychiatry. 67 (3): 415–20. PMID 16649828. doi:10.4088/JCP.v67n0312.
^ Carpenter LL, Milosavljevic N, Schecter JM, Tyrka AR, Price LH (October 2005). "Augmentation with open-label atomoxetine for partial or non-response to antidepressants". The Journal of Clinical Psychiatry. 66 (10): 1234–8. PMID 16259536. doi:10.4088/JCP.v66n1005.
^ Kratochvil CJ, Newcorn JH, Arnold LE, Duesenberg D, Emslie GJ, Quintana H, Sarkis EH, Wagner KD, Gao H, Michelson D & Biederman J (September 2005). "Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms". Journal of the American Academy of Child and Adolescent Psychiatry. 44 (9): 915–24. PMID 16113620. doi:10.1097/01.chi.0000169012.81536.38.

External links

RxList.com – Strattera
Detailed Strattera Consumer Information: Uses, Precautions, Side Effects
All disclosed Lilly trials
Strattera Related Published Studies

UpToDate Contents

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1. 小児および思春期における注意欠陥多動性障害治療薬の薬理学 pharmacology of drugs used to treat attention deficit hyperactivity disorder in children and adolescents
2. 成人の注意欠陥多動性障害（ADHD）に対する薬物療法 pharmacotherapy for adult attention deficit hyperactivity disorder
3. 小児および思春期における注意欠陥多動性障害：薬物治療 attention deficit hyperactivity disorder in children and adolescents treatment with medications
4. 注意欠陥多動性障害に対する薬物療法を受けた患者の心臓評価 cardiac evaluation of patients receiving pharmacotherapy for attention deficit hyperactivity disorder
5. 成人における単極性大うつ病：刺激薬および stimulant-like drugsによる抗うつ薬の増強 unipolar major depression in adults augmentation of antidepressants with stimulants and stimulant like drugs

English Journal

Differences in maintenance of response upon discontinuation across medication treatments in attention-deficit/hyperactivity disorder.

Buitelaar J1, Asherson P2, Soutullo C3, Colla M4, Adams DH5, Tanaka Y5, Haynes VS5, Escobar R5, Upadhyaya H6.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology.Eur Neuropsychopharmacol.2015 Oct;25(10):1611-21. doi: 10.1016/j.euroneuro.2015.06.003. Epub 2015 Jun 22.
The attention-deficit/hyperactivity disorder (ADHD) treatment literature has been focused on onset-of-effect and short-term effect size, with little exploration of ADHD symptoms upon medication discontinuation. The objective of this narrative review and analysis was to better understand the relapse
PMID 26169574

Melt-in-Mouth Multi-particulate System for the Treatment of ADHD: A Convenient Platform for Pediatric Use.

Patadia J1, Tripathi R2,3, Joshi A4,5.
AAPS PharmSciTech.AAPS PharmSciTech.2015 Sep 21. [Epub ahead of print]
Generally, pellets obtained from extrusion/spheronization, containing microcrystalline cellulose (MCC), do not disintegrate. An attempt has been made to develop melt-in-mouth pellets of taste-masked atomoxetine hydrochloride, using extrusion-spheronization, for pediatric patients. Melt-in-mouth pell
PMID 26392403

Pediatric Priapism Secondary to Psychotherapeutic Medications.

Armstrong WR1, Grimsby GM2, Jacobs MA3.
Urology.Urology.2015 Aug;86(2):376-8. doi: 10.1016/j.urology.2015.05.006. Epub 2015 Jul 18.
With the increased application of many different drug classes for the treatment of psychiatric conditions in children, the incidence of priapism has also increased. Priapism of pharmacotherapeutic etiology in the pediatric population is a complex and poorly understood entity that continues to presen
PMID 26199163

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★リンクテーブル★

リンク元	「アトモキセチン」「塩酸アトモキセチン」
関連記事	「hydrochloride」

「アトモキセチン」

Atomoxetine
Clinical data
Trade names	Strattera
AHFS/Drugs.com	Monograph
MedlinePlus	a603013
Pregnancy; category	AU: B3; US: C (Risk not ruled out); ;
Routes of; administration	By mouth
ATC code	N06BA09 (WHO);
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	63 to 94%
Protein binding	98%
Metabolism	Hepatic, via CYP2D6
Biological half-life	5.2 hours
Excretion	Renal (80%) and faecal (17%)
Identifiers
	IUPAC name (3R)-N-Methyl-3-(2-methylphenoxy)-3-phenylpropan-1-amine;
Synonyms	(R)-N-Methyl-3-phenyl-3-(o-tolyloxy)propan-1-amine
CAS Number	83015-26-3 ;
PubChem CID	54841;
IUPHAR/BPS	7118;
DrugBank	DB00289 ;
ChemSpider	49516 ;
UNII	ASW034S0B8;
KEGG	D07473 ;
ChEBI	CHEBI:127342 ;
ChEMBL	CHEMBL641 ;
ECHA InfoCard	100.158.200
Chemical and physical data
Formula	C17H21NO
Molar mass	255.36 g/mol; 291.81 g/mol (hydrochloride)
3D model (JSmol)	Interactive image;
	SMILES CC1=C(C=CC=C1)O[C@H](CCNC)C2=CC=CC=C2 ;
	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 ; Key:VHGCDTVCOLNTBX-QGZVFWFLSA-N ;
(what is this?) (verify)

　　[★]

英: atomoxetine
化: 塩酸アトモキセチン atomoxetine hydrochloride
商: ストラテラ Strattera
関: 精神神経用剤

「塩酸アトモキセチン」

　　[★]

英: atomoxetine hydrochloride
関: アトモキセチン

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[MSR-1] ^ ^a ^b ^c ^d ^e ^f "atomoxetine (Rx) – Strattera". Medscape Reference. WebMD. Retrieved 10 November 2013.

[TGA-2] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q "STRATTERA® (atomoxetine hydrochloride)". TGA eBusiness Services. Eli Lilly Australia Pty. Limited. 21 August 2013. Retrieved 10 November 2013.

[DM-3] ^ ^a ^b ^c ^d ^e ^f ^g "ATOMOXETINE HYDROCHLORIDE capsule [Mylan Pharmaceuticals Inc.]". DailyMed. Mylan Pharmaceuticals Inc. October 2011. Retrieved 10 November 2013.

[PI-4] ^ ^a ^b ^c ^d ^e ^f "STRATTERA^® (atomoxetine hydrochloride) CAPSULES for Oral Use. Full Prescribing Information" (PDF). Indianapolis, USA: Eli Lilly and Company. 20 February 2014. Retrieved 23 May 2014.

[5] "Press Announcements - FDA approves first generic Strattera for the treatment of ADHD". www.fda.gov. Retrieved 2 June 2017.

[6] Ghuman, Jaswinder K.; Hutchison, Shari L. (2014-11-01). "Atomoxetine is a second-line medication treatment option for ADHD". Evidence Based Mental Health. 17 (4): 108–108. ISSN 1468-960X. PMID 25165169. doi:10.1136/eb-2014-101805.

[Maudsley-7] Taylor, D; Paton, C; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 978-0-470-97948-8.

[8] Kooij, JJS (2013). Adult ADHD Diagnostic Assessment and Treatment (PDF). Springer London. ISBN 978-1-4471-4137-2. doi:10.1007/978-1-4471-4138-9.

[EMC-9] "Strattera 10mg, 18mg, 25mg, 40mg, 60mg, 80mg or 100mg hard capsules". electronic Medicines Compendium. 28 May 2013. Retrieved 10 November 2013.

[10] "Strattera Product Insert". Retrieved 8 December 2013.

[FDA-11] "STRATTERA Medication Guide" (PDF). Eli Lilly and Company. 2003. Retrieved 17 December 2013.

[12] "Atomoxetine and suicidality in children and adolescents". Australian Prescriber. 36 (5). October 2013. p. 166. Archived from the original on 10 November 2013. Retrieved 10 November 2013.

[CYP2D6-13] Horn, John R.; Hansten, Philip D. (2008). "Get to Know an Enzyme: CYP2D6". Pharmacy Times. Retrieved 19 February 2015.

[14] Baselt, Randall C. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 118–20. ISBN 0-931890-08-X.

[PDSP-15] Roth, BL; Driscol, J (12 January 2011). "PDSP K_i Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 8 November 2013. Retrieved 10 November 2013.

[NPP2002-16] Bymaster, FP; Katner, JS; Nelson, DL; Hemrick-Luecke, SK; Threlkeld, PG; Heiligenstein, JH; Morin, SM; Gehlert, DR; Perry, KW (November 2002). "Atomoxetine Increases Extracellular Levels of Norepinephrine and Dopamine in Prefrontal Cortex of Rat: A Potential Mechanism for Efficacy in Attention Deficit/Hyperactivity Disorder" (PDF). Neuropsychopharmacology. 27 (5): 699–711. PMID 12431845. doi:10.1016/S0893-133X(02)00346-9.

[17] Stahl, Stephen M. (17 March 2008). "17". Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (3rd ed.). New York: Cambridge University Press. p. 891. ISBN 9780521673761. Retrieved 1 November 2015. Since the prefrontal cortex lacks high concentrations of DAT, DA is inactivated in this part of the brain by NET. Thus, inhibiting NET increases both DA and NE in the prefrontal cortex (Figures 12-36 and 17-21). However, since there are only a few NE neurons and NETs in nucleus accumbens, inhibiting NET does not lead to an increase in either NE or DA there (Figure 17-21). For this reason, in ADHD patients with deficient arousal and weak NE and DA signals in prefrontal cortex, a selective NRI such as atomoxetine increases both NE and DA in prefrontal cortex, enhancing tonic signaling of both, but it increases neither NE nor DA in the nucleus accumbens. Therefore atomoxetine has no abuse potential.

[DingNaganawa2014-18] Ding, Y.-S.; Naganawa, M.; Gallezot, J.-D.; Nabulsi, N.; Lin, S.-F.; Ropchan, J.; Weinzimmer, D.; McCarthy, T.J.; Carson, R.E.; Huang, Y.; Laruelle, M. (2014). "Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD". NeuroImage. 86: 164–171. ISSN 1053-8119. PMID 23933039. doi:10.1016/j.neuroimage.2013.08.001. The noradrenergic action also exerts an important clinical effect in different antidepressant classes such as desipramine and nortriptyline (tricyclics, prevalent noradrenergic effect), reboxetine and atomoxetine (relatively pure noradrenergic reuptake inhibitor (NRIs)), and dual action antidepressants such as the serotonin noradrenaline reuptake inhibitors (SNRIs), the noradrenergic and dopaminergic reuptake inhibitor (NDRI) bupropion, and other compounds (e.g., mianserin, mirtazapine), which enhance the noradrenergic transmission

[19] Ludolph, AG; Udvardi, PT; Schaz, U; Henes, C; Adolph, O; Weigt, HU; Fegert, JM; Boeckers, TM; Föhr, KJ (May 2010). "Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations" (PDF). British Journal of Pharmacology. 160 (2): 283–291. PMC 2874851 . PMID 20423340. doi:10.1111/j.1476-5381.2010.00707.x.

[20] Lesch, KP; Merker, S; Reif, A; Novak, M (June 2013). "Dances with black widow spiders: dysregulation of glutamate signalling enters centre stage in ADHD". European Neuropsychopharmacology. 23 (6): 479–491. PMID 22939004. doi:10.1016/j.euroneuro.2012.07.013.

[21] "New gene study of ADHD points to defects in brain signaling pathways". Children's Hospital of Philadelphia. 4 December 2011.

[pmid15225731-22] Creighton, CJ; Ramabadran, K; Ciccone, PE; Liu, J; Orsini, MJ; Reitz, AB (2 August 2004). "Synthesis and biological evaluation of the major metabolite of atomoxetine: elucidation of a partial kappa-opioid agonist effect.". Bioorganic & Medicinal Chemistry Letters. 14 (15): 4083–5. PMID 15225731. doi:10.1016/j.bmcl.2004.05.018.

[23] Kobayashi, T; Washiyama, K; Ikeda, K (Jun 2010). "Inhibition of G-protein-activated inwardly rectifying K+ channels by the selective norepinephrine reuptake inhibitors atomoxetine and reboxetine.". Neuropsychopharmacology. 35 (7): 1560–9. PMC 3055469 . PMID 20393461. doi:10.1038/npp.2010.27.

[24] Bymaster, FP; Katner, JS; Nelson, DL; Hemrick-Luecke, SK; Threlkeld, PG; Heiligenstein, JH; Morin, SM; Gehlert, DR; Perry, KW (November 2002). "Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder". Neuropsychopharmacology. 27 (5): 699–711. PMID 12431845. doi:10.1016/S0893-133X(02)00346-9.

[orangeBook-25] "Patent and Exclusivity Search Results". Electronic Orange Book. US Food and Drug Administration. Retrieved 26 April 2009.

[26] [FDA.org/news events/newsroom/press announcements/ucm561096.htm FDA.org/news events/newsroom/press announcements/ucm561096.htm] Check |url= value (help). Missing or empty |title= (help)

[27] "Drugmaker Eli Lilly loses patent case over ADHD drug, lowers revenue outlook". Chicago Tribune.

[28] "Sun Pharma receives USFDA approval for generic Strattera capsules". International Business Times. Archived from the original on 7 April 2011.

[29] "Sun Pharma Q1 2011-12 Earnings Call Transcript 10.00 am, July 29, 2011" (PDF). Archived from the original (PDF) on 29 September 2011.

[30] Spencer TJ, Faraone SV, Michelson D, Adler LA, Reimherr FW, Glatt SJ & Biederman J (March 2006). "Atomoxetine and adult attention-deficit/hyperactivity disorder: the effects of comorbidity". The Journal of Clinical Psychiatry. 67 (3): 415–20. PMID 16649828. doi:10.4088/JCP.v67n0312.

[31] Carpenter LL, Milosavljevic N, Schecter JM, Tyrka AR, Price LH (October 2005). "Augmentation with open-label atomoxetine for partial or non-response to antidepressants". The Journal of Clinical Psychiatry. 66 (10): 1234–8. PMID 16259536. doi:10.4088/JCP.v66n1005.

[32] Kratochvil CJ, Newcorn JH, Arnold LE, Duesenberg D, Emslie GJ, Quintana H, Sarkis EH, Wagner KD, Gao H, Michelson D & Biederman J (September 2005). "Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms". Journal of the American Academy of Child and Adolescent Psychiatry. 44 (9): 915–24. PMID 16113620. doi:10.1097/01.chi.0000169012.81536.38.

v t e Opioid receptor modulators
MOR	Agonists (abridged; see here for a full list): 7-Acetoxymitragynine 7-Hydroxymitragynine ψ-Akuammigine α-Chlornaltrexamine α-Narcotine Acetyldihydrocodeine Acetylfentanyl Acrylfentanyl Adrenorphin (metorphamide) AH-7921 Akuammicine Akuammidine Alfentanil Anileridine Apparicine β-Endorphin BAM-12P BAM-18P BAM-22P Benzhydrocodone Benzylmorphine Bezitramide Biphalin BU08070 Buprenorphine Butorphan Butorphanol Butyrfentanyl BW-373U86 Carfentanil Casokefamide Cebranopadol Chloroxymorphamine Codeine DADLE DAMGO (DAGO) Dermorphin Desomorphine Dextromoramide Dextropropoxyphene (propoxyphene) Dezocine Dimenoxadol Dimethylaminopivalophenone Eluxadoline Diamorphine (heroin) Dihydrocodeine Dihydroetorphine Dihydromorphine Diphenoxylate Dipipanone Dynorphin A Embutramide Endomorphin-1 Endomorphin-2 Eseroline Ethylmorphine Etorphine Fentanyl Fluorophen Frakefamide Furanylfentanyl Hemorphin-4 Herkinorin Hodgkinsine Hydrocodone Hydromorphinol Hydromorphone IBNtxA Ketamine Ketobemidone Kratom Laudanosine Lefetamine Leu-enkephalin Levacetylmethadol Levomethorphan Levorphanol Lexanopadol Loperamide Matrine Meptazinol Met-enkephalin (metenkefalin) Methadone Metkefamide Metopon Mitragynine Mitragynine pseudoindoxyl Morphiceptin Morphine Nalbuphine Nalbuphine sebacate NalBzOH Nalmexone Naltalimide Neopine NFEPP Nicocodeine Nicodicodeine Nicomorphine NKTR-181 Norketamine O-Desmethyltramadol Octreotide Oliceridine OM-3-MNZ Oripavine Oxycodone Oxymorphazone Oxymorphonazine Oxymorphone Oxymorphone phenylhydrazone OxyPNPH Papaver somniferum (opium) Pentazocine Pericine Pethidine (meperidine) Phenazocine Phencyclidine Piminodine Piritramide PL-017 Prodine Propiram PZM21 Racemethorphan Racemorphan Remifentanil Salsolinol SC-17599 Sinomenine Sufentanil Tapentadol Tetrahydropapaveroline TH-030418 Thebaine Thienorphine Tianeptine Tilidine Tramadol Trimebutine TRIMU 5 TRV734 Tubotaiwine U-47700 Valorphin Viminol Xorphanol PAMs: BMS-986121 BMS-986122 Antagonists: (3S,4S)-Picenadol 2-(S)-N,N-(R)-Viminol 4-Caffeoyl-1,5-quinide 4′-Hydroxyflavanone 4',7-Dihydroxyflavone 6β-Naltrexol 6β-Naltrexol-d4 18-MC α-Gliadin β-Chlornaltrexamine β-Funaltrexamine Akuammine Alvimopan AM-251 Apigenin AT-076 Axelopran Bevenopran Catechin Catechin gallate Clocinnamox CTAP CTOP Cyclofoxy Cyprodime Diacetylnalorphine Diprenorphine ECG EGC Epicatechin Eptazocine Gemazocine Ginsenoside R Hyperoside Ibogaine Levallorphan Lobeline LY-255582 LY-2196044 Methocinnamox Methylnaltrexone Methylsamidorphan chloride Naldemedine Nalmefene Nalodeine (N-allylnorcodeine) Nalorphine Nalorphine dinicotinate Naloxazone Naloxegol Naloxol Naloxonazine Naloxone Naltrexazone Naltrexonazine Naltrexone Naltrindole Naringenin Noribogaine Oxilorphan Pawhuskin A Rimonabant Quadazocine Samidorphan Taxifolin Unknown/unsorted: Cannabidiol Coronaridine Cyproterone acetate Dihydroakuuamine Tabernanthine Tetrahydrocannabinol
DOR	Agonists: 6'-GNTI 7-SIOM ADL-5747 (PF-04856881) ADL-5859 Alazocine (SKF-10047) Amoxapine AR-M100390 (ARM390) AZD2327 β-Endorphin BAM-18P Biphalin BU-48 Butorphan Butorphanol BW-373U86 Casokefamide Cebranopadol Codeine Cyclazocine DADLE Deltorphin A Deltorphin I Deltorphin II Desmethylclozapine Dezocine Diamorphine (heroin) Dihydroetorphine Dihydromorphine DPDPE DPI-221 DPI-3290 DSLET Ethylketazocine Etorphine Fentanyl FIT Fluorophen Hemorphin-4 Hydrocodone Hydromorphone Ibogaine Isomethadone JNJ-20788560 KNT-127 Kratom Laudanosine Leu-enkephalin Levomethorphan Levorphanol Lexanopadol Lofentanil Met-enkephalin (metenkefalin) Metazocine Metkefamide Mitragynine Mitragynine pseudoindoxyl Morphine N-Phenethyl-14-ethoxymetopon Norbuprenorphine NalBzOH O-Desmethyltramadol Oripavine Oxycodone Oxymorphone Pethidine (meperidine) Proglumide Racemethorphan Racemorphan RWJ-394674 Samidorphan SB-235863 SNC-80 SNC-162 TAN-67 (SB-205,607) TH-030418 Thebaine Thiobromadol (C-8813) Tianeptine Tonazocine Tramadol TRV250 Xorphanol Zenazocine Antagonists: 4',7-Dihydroxyflavone 5'-NTII 6β-Naltrexol 6β-Naltrexol-d4 α-Santolol β-Chlornaltrexamine Apigenin AT-076 Axelopran Bevenopran BNTX Catechin Catechin gallate Clocinnamox Diacetylnalorphine Diprenorphine ECG EGC Eluxadoline Epicatechin ICI-154129 ICI-174864 LY-255582 LY-2196044 Methylnaltrexone Methylnaltrindole N-Benzylnaltrindole Nalmefene Nalorphine Naltrexone Naltriben Naltrindole Naloxone Naringenin Noribogaine Pawhuskin A Quadazocine SDM25N SoRI-9409 Taxifolin Thienorphine Unknown/unsorted: 18-MC Cannabidiol Coronaridine Cyproterone acetate Tabernanthine Tetrahydrocannabinol
KOR	Agonists: 6'-GNTI 8-CAC 18-MC 14-Methoxymetopon β-Chlornaltrexamine β-Funaltrexamine Adrenorphin (metorphamide) Akuuamicine Alazocine (SKF-10047) Allomatrine Apadoline Asimadoline BAM-12P BAM-18P BAM-22P Big dynorphin Bremazocine BRL-52537 Butorphan Butorphanol BW-373U86 Cebranopadol Ciprefadol CR665 Cyclazocine Cyclorphan Cyprenorphine Diamorphine (heroin) Diacetylnalorphine Difelikefalin Dihydroetorphine Dihydromorphine Diprenorphine Dynorphin A Dynorphin B (rimorphin) Eluxadoline Enadoline Eptazocine Erinacine E Ethylketazocine Etorphine Fedotozine Fentanyl Gemazocine GR-89696 GR-103545 Hemorphin-4 Herkinorin HS665 Hydromorphone HZ-2 Ibogaine ICI-199,441 ICI-204,448 Ketamine Ketazocine Laudanosine Leumorphin (dynorphin B-29) Levallorphan Levomethorphan Levorphanol Lexanopadol Lofentanil LPK-26 Lufuradom Matrine MB-1C-OH Menthol Metazocine Metkefamide Mianserin Mirtazapine Morphine Moxazocine MR-2034 N-MPPP Nalbuphine Nalbuphine sebacate NalBzOH Nalfurafine Nalmefene Nalodeine (N-allylnorcodeine) Nalorphine Naltriben Niravoline Norbuprenorphine Norbuprenorphine-3-glucuronide Noribogaine Norketamine O-Desmethyltramadol Oripavine Oxilorphan Oxycodone Pentazocine Pethidine (meperidine) Phenazocine Proxorphan Racemethorphan Racemorphan RB-64 Salvinorin A (salvia) Salvinorin B ethoxymethyl ether Salvinorin B methoxymethyl ether Samidorphan Spiradoline (U-62,066) TH-030418 Thienorphine Tifluadom Tricyclic antidepressants (e.g., amitriptyline, desipramine, imipramine, nortriptyline) U-50,488 U-54,494A U-69,593 Xorphanol Antagonists: 4′-Hydroxyflavanone 4',7-Dihydroxyflavone 5'-GNTI 6'-GNTI 6β-Naltrexol 6β-Naltrexol-d4 β-Chlornaltrexamine Buprenorphine/samidorphan Amentoflavone ANTI Apigenin Arodyne AT-076 Axelopran AZ-MTAB Binaltorphimine BU09059 Buprenorphine Catechin Catechin gallate CERC-501 (LY-2456302) Clocinnamox Cyclofoxy Dezocine DIPPA EGC ECG Epicatechin Hyperoside JDTic LY-255582 LY-2196044 LY-2444296 LY-2459989 LY-2795050 MeJDTic Methylnaltrexone ML190 ML350 MR-2266 N-Fluoropropyl-JDTic Naloxone Naltrexone Naltrindole Naringenin Norbinaltorphimine Noribogaine Pawhuskin A PF-4455242 RB-64 Quadazocine Taxifolin UPHIT Zyklophin Unknown/unsorted: Akuammicine Akuammine Coronaridine Cyproterone acetate Dihydroakuuamine Ibogamine Tabernanthine
NOP	Agonists: (Arg14,Lys15)Nociceptin ((pF)Phe⁴)Nociceptin(1-13)NH₂ (Phe¹Ψ(CH₂-NH)Gly²)Nociceptin(1-13)NH₂ Ac-RYYRWK-NH₂ Ac-RYYRIK-NH₂ BU08070 Buprenorphine Cebranopadol Dihydroetorphine Etorphine JNJ-19385899 Levomethorphan Levorphanol Levorphanol Lexanopadol MCOPPB MT-7716 NNC 63-0532 Nociceptin (orphanin FQ) Nociceptin (1-11) Nociceptin (1-13)NH₂ Norbuprenorphine Racemethorphan Racemorphan Ro64-6198 Ro65-6570 SCH-221510 SCH-486757 SR-8993 SR-16435 TH-030418 Antagonists: (Nphe¹)Nociceptin(1-13)NH₂ AT-076 BAN-ORL-24 J-113397 JTC-801 LY-2940094 NalBzOH Nociceptin (1-7) Nocistatin SB-612111 SR-16430 Thienorphine Trap-101 UFP-101
Unsorted	β-Casomorphins Amidorphin BAM-20P Cytochrophin-4 Deprolorphin Gliadorphin (gluteomorphin) Gluten exorphins Hemorphins Kava constituents MEAGL MEAP NEM Neoendorphins Nepetalactone (catnip) Peptide B Peptide E Peptide F Peptide I Rubiscolins Soymorphins
Others	Enkephalinase inhibitors: Amastatin BL-2401 Candoxatril D -Phenylalanine Dexecadotril (retorphan) Ecadotril (sinorphan) Kelatorphan Racecadotril (acetorphan) RB-101 RB-120 RB-3007 Opiorphan Selank Semax Spinorphin Thiorphan Tynorphin Ubenimex (bestatin) Propeptides: β-Lipotropin (proendorphin) Prodynorphin Proenkephalin Pronociceptin Proopiomelanocortin (POMC) Others: Kyotorphin (met-enkephalin releaser/degradation stabilizer)
See also: Receptor/signaling modulators • Signaling peptide/protein receptor modulators

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atomoxetine hydrochloride