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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/08/18 19:18:59」(JST)

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Atomoxetine (brand name: Strattera) is a serotonin-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]

1 Medical uses
- 1.1 Attention deficit hyperactivity disorder
2 Contraindications
3 Adverse effects
4 Overdose
5 Interactions
6 Pharmacology
- 6.1 Pharmacodynamics
- 6.2 Pharmacokinetics
- 6.3 Pharmacogenomics
7 Chemistry
- 7.1 Synthesis
- 7.2 Detection in biological fluids
8 History
9 Brand names
10 Research
11 See also
12 References
13 External links

Medical uses

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]

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

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]

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]

Interactions

Atomoxetine is a substrate for CYP2D6. Concurrent treatment with a CYP2D6 inhibitor such as bupropion, fluoxetine, or paroxetine has been shown to increase plasma atomoxetine by 100% or more, as well as increase N-desmethylatomoxetine levels and decrease plasma 4-hydroxyatomoxetine levels by a similar degree.^[13]^[14]^[15]

Atomoxetine has been found to directly inhibit hERG potassium currents with an IC₅₀ of 6.3 μM, which has the potential to cause arrhythmia.^[14]^[16] QT prolongation has been reported with atomoxetine at therapeutic doses and in overdose; it is suggested that atomoxetine not be used with other medications that may prolong the QT interval, concomitantly with CYP2D6 inhibitors, and caution to be used in poor metabolizers.^[14]

Other notable drug interactions include:^[2]

Antihypertensive agents, due to atomoxetine acting as an indirect sympathomimetic
Indirect-acting sympathomimetics, such as pseudoephedrine, norepinephrine reuptake inhibitors, or MAOIs
Direct-acting sympathomimetics, such as phenylephrine or other α₁ adrenoceptor agonists, including pressors such as dobutamine or isoprenaline and β₂ adrenoceptor agonists
Highly plasma protein-bound drugs: atomoxetine has the potential to displace these drugs from plasma proteins which may potentiate their adverse or toxic effects. In vitro, atomoxetine does not affect the plasma protein binding of aspirin, desipramine, diazepam, paroxetine, phenytoin, or warfarin^[17]^[18]

Pharmacology

Pharmacodynamics

Atomoxetine inhibits the presynaptic norepinephrine transporter, preventing the reuptake of norepinephrine throughout the brain along with inhibiting the reuptake of dopamine in specific brain regions such as the prefrontal cortex, where dopamine transporter expression is minimal.^[17] In rats, atomoxetine increased prefrontal cortex catecholamine concentrations without altering dopamine levels in the striatum or nucleus accumbens; in contrast, methylphenidate was found to increase prefrontal, striatal, and accumbal dopamine levels to the same degree.^[19] In mice, atomoxetine was also found to increase prefrontal catecholamine levels without affecting striatal or accumbal levels.^[20]

Atomoxetine's status as a SERT inhibitor at clinical doses in humans is uncertain. A PET imaging study on rhesus monkeys found that atomoxetine occupied >90% and >85% of neural norepinephrine and serotonin transporters, respectively.^[21] However, both mouse and rat microdialysis studies have failed to find an increase in extracellular serotonin in the prefrontal cortex following acute or chronic atomoxetine treatment.^[19]^[20]

Atomoxetine has been found to act as an NMDA antagonist in rat cortical neurons at therapeutic concentrations.^[22]^[23] It causes a use-dependent open-channel block and its binding site overlaps with the Mg²⁺ binding site.^[22]^[23] Atomoxetine's ability to increase prefrontal cortex firing rate in anesthetized rats could not be blocked by D₁ or α₁ receptor antagonists, but could be potentiated by NMDA or an α₂ receptor antagonist, suggesting a glutamatergic mechanism.^[24] In Sprague Dawley rats, atomoxetine reduces NR2B protein content without altering transcript levels.^[25] Aberrant glutamate and NMDA receptor function have been implicated in the etiology of ADHD.^[26]^[27]

Atomoxetine also reversibly inhibits GIRK currents in Xenopus oocytes in a concentration-dependent, voltage-independent, and time-independent manner.^[28] K_ir3.1/3.2 ion channels are opened downstream of M₂, α₂, D₂, and A₁ stimulation, as well as other G_i-coupled receptors.^[28] Therapeutic concentrations of atomoxetine are within range of interacting with GIRKs, especially in CYP2D6 poor metabolizers.^[28] It is not known whether this contributes to the therapeutic effects of atomoxetine in ADHD.

4-hydroxyatomoxetine, the major active metabolite of atomoxetine in CYP2D6 extensive metabolizers, has been found to have sub-micromolar affinity for opioid receptors, acting as an antagonist at μ-opioid receptors and a partial agonist at κ-opioid receptors.^[29] It is not known whether this contributes to the therapeutic effects of atomoxetine in ADHD.

**Binding profile of atomoxetine and its metabolites**^[30]^[19]^[29]^[31]^[17]^[18]
Protein	K_i (nM) for atomoxetine	K_i (nM) for 4-hydroxyatomoxetine	K_i (nM) for N-desmethylatomoxetine
SERT	77	43	?
5-HT_1A	>1,000	?	?
5-HT_1B	>1,000	?	?
5-HT_1D	>1,000	?	?
5-HT₂	2,000	1,000	1,700
5-HT₆	>1,000	?	?
5-HT₇	>1,000	?	?
NET	5	3	92
α₁	11,400	20,000	19,600
α_2A	29,800	>30,000	>10,000
β₁	18,000	56,100	32,100
M₁	>100,000	>100,000	>100,000
M₂	>100,000	>100,000	>100,000
DAT	1451	?	?
D₁	>10,000	>10,000	>10,000
D₂	>10,000	>10,000	>10,000
H₁	12,100	>100,000	>100,000
GABA_A	200	>30,000	>10,000
NMDA	3,470^a	?	?
δOR	?	300	?
κOR	?	95	?
μOR	?	422	?
σ₁	>1,000	?	?
K_ir3.1/3.2	10,900^b	?	?
K_ir3.2	12,400^b	?	?
K_ir3.1/3.4	6,500^b	?	?
hERG	6,300	20,000	5,710

All values are for human receptors unless otherwise specified.

^arat cortex

^bXenopus oocytes

Pharmacokinetics

Orally administered atomoxetine is rapidly and completely absorbed.^[17] Hepatic first-pass metabolism is dependent on CYP2D6 activity, resulting in an absolute bioavailability of 63% for extensive metabolizers and 94% for poor metabolizers.^[17] Maximum plasma concentration is reached in 1-2 hours.^[17] If taken with food, the maximum plasma concentration decreases by 10-40% and delays the t_max by 1 hour.^[17] Drugs affecting gastric pH have no effect on oral bioavailability.^[32]

Atomoxetine has a volume of distribution of 0.85 L/kg, with limited partitioning into red blood cells.^[17] It is highly bound to plasma proteins (98.7%), mainly albumin, along with α₁-acid glycoprotein (77%) and IgG (15%).^[17]^[18] Its metabolite N-desmethylatomoxetine is 99.1% bound to plasma proteins, while 4-hydroxyatomoxetine is only 66.6% bound.^[17]

The half-life of atomoxetine varies widely between individuals, with an average range of 4.5 to 19 hours.^[17]^[33] As atomoxetine is metabolized by CYP2D6, exposure may be increased 10-fold in CYP2D6 poor metabolizers.^[33]

Atomoxetine, N-desmethylatomoxetine, and 4-hydroxyatomoxetine produce minimal to no inhbition of CYP1A2 and CYP2C9, but inhibit CYP2D6 in human liver microsomes at concentrations between 3.6-17 μmol/L.^[17] Plasma concentrations of 4-hydroxyatomoxetine and N-desmethylatomoxetine at steady state are 1.0% and 5% that of atomoxetine in CYP2D6 extensive metabolizers, and are 5% and 45% that of atomoxetine in CYP2D6 poor metabolizers.^[32]

Atomoxetine is excreted unchanged in urine at <3% in both extensive and poor CYP2D6 metabolizers, with >96% and 80% of a total dose being excreted in urine, respectively.^[17] The fractions excreted in urine as 4-hydroxyatomoxetine and its glucuronide account for 86% of a given dose in extensive metabolizers, but only 40% in poor metabolizers.^[17] CYP2D6 poor metabolizers excrete greater amounts of minor metabolites, namely N-desmethylatomoxetine and 2-hydroxymethylatomoxetine and their conjugates.^[17]

Major metabolites of atomoxetine in humans.^[17]

Pharmacogenomics

Chinese adults homozygous for the hypoactive CYP2D6*10 allele have been found to exhibit two-fold higher AUCs and 1.5-fold higher maximum plasma concentrations compared to extensive metabolizers.^[17]

Japanese men homozygous for CYP2D6*10 have similarly been found to experience two-fold higher AUCs compared to extensive metabolizers.^[17]

Chemistry

Atomoxetine, or (−)-methyl[(3R)-3-(2-methylphenoxy)-3-phenylpropyl]amine, is a white, granular powder that is highly soluble in water.

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

Synthesis

Original synthesis of atomoxetine, as patented by Eli Lilly and Company^[34]^[35]

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.^[36]

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. Its patent expired in May 2017.^[37] On May 30, 2017 the FDA approved the generic production by four pharmaceutical companies.^[38] 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.^[39] On 1 September 2010, Sun Pharmaceuticals announced it would begin manufacturing a generic in the United States.^[40] 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."^[41]

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.^[42]^[43]^[44]

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 "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.
^ Todor, I; Popa, A; Neag, M; Muntean, D; Bocsan, C; Buzoianu, A; Vlase, L; Gheldiu, AM; Briciu, C (NaN). "Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers.". Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques. 19 (2): 198–207. PMID 27518170. Check date values in: |date= (help)
^ ^a ^b ^c Kasi, PM; Mounzer, R; Gleeson, GH (2011). "Cardiovascular side effects of atomoxetine and its interactions with inhibitors of the cytochrome p450 system.". Case reports in medicine. 2011: 952584. PMID 21765848. doi:10.1155/2011/952584.
^ Belle, DJ; Ernest, CS; Sauer, JM; Smith, BP; Thomasson, HR; Witcher, JW (November 2002). "Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics.". Journal of clinical pharmacology. 42 (11): 1219–27. PMID 12412820.
^ Scherer, D; Hassel, D; Bloehs, R; Zitron, E; von Löwenstern, K; Seyler, C; Thomas, D; Konrad, F; Bürgers, HF; Seemann, G; Rottbauer, W; Katus, HA; Karle, CA; Scholz, EP (January 2009). "Selective noradrenaline reuptake inhibitor atomoxetine directly blocks hERG currents.". British journal of pharmacology. 156 (2): 226–36. PMID 19154426. doi:10.1111/j.1476-5381.2008.00018.x.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r Sauer, JM; Ring, BJ; Witcher, JW (2005). "Clinical pharmacokinetics of atomoxetine.". Clinical pharmacokinetics. 44 (6): 571–90. PMID 15910008. doi:10.2165/00003088-200544060-00002.
^ ^a ^b ^c "21-411 Strattera Clinical Pharmacology Biopharmaceutics Review Part 2" (PDF).
^ ^a ^b ^c 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.
^ ^a ^b Koda, K; Ago, Y; Cong, Y; Kita, Y; Takuma, K; Matsuda, T (July 2010). "Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice.". Journal of neurochemistry. 114 (1): 259–70. PMID 20403082. doi:10.1111/j.1471-4159.2010.06750.x.
^ 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
^ ^a ^b 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.
^ ^a ^b Barygin, OI; Nagaeva, EI; Tikhonov, DB; Belinskaya, DA; Vanchakova, NP; Shestakova, NN (1 April 2017). "Inhibition of the NMDA and AMPA receptor channels by antidepressants and antipsychotics.". Brain research. 1660: 58–66. PMID 28167075. doi:10.1016/j.brainres.2017.01.028.
^ Di Miceli, M; Gronier, B (June 2015). "Psychostimulants and atomoxetine alter the electrophysiological activity of prefrontal cortex neurons, interaction with catecholamine and glutamate NMDA receptors.". Psychopharmacology. 232 (12): 2191–205. PMID 25572531. doi:10.1007/s00213-014-3849-y.
^ Udvardi, PT; Föhr, KJ; Henes, C; Liebau, S; Dreyhaupt, J; Boeckers, TM; Ludolph, AG (2013). "Atomoxetine affects transcription/translation of the NMDA receptor and the norepinephrine transporter in the rat brain--an in vivo study.". Drug design, development and therapy. 7: 1433–46. PMID 24348020. doi:10.2147/DDDT.S50448.
^ Maltezos, S; Horder, J; Coghlan, S; Skirrow, C; O'Gorman, R; Lavender, TJ; Mendez, MA; Mehta, M; Daly, E; Xenitidis, K; Paliokosta, E; Spain, D; Pitts, M; Asherson, P; Lythgoe, DJ; Barker, GJ; Murphy, DG (18 March 2014). "Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study.". Translational psychiatry. 4: e373. PMID 24643164. doi:10.1038/tp.2014.11.
^ Chang, JP; Lane, HY; Tsai, GE (2014). "Attention deficit hyperactivity disorder and N-methyl-D-aspartate (NMDA) dysregulation.". Current pharmaceutical design. 20 (32): 5180–5. PMID 24410567.
^ ^a ^b ^c Kobayashi, T; Washiyama, K; Ikeda, K (June 2010). "Inhibition of G-protein-activated inwardly rectifying K+ channels by the selective norepinephrine reuptake inhibitors atomoxetine and reboxetine.". Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 35 (7): 1560–9. PMID 20393461. doi:10.1038/npp.2010.27.
^ ^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.
^ 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.
^ 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.
^ ^a ^b "Strattera Package Insert" (PDF). FDA.
^ ^a ^b Brown, JT; Bishop, JR (2015). "Atomoxetine pharmacogenetics: associations with pharmacokinetics, treatment response and tolerability.". Pharmacogenomics. 16 (13): 1513–20. PMID 26314574. doi:10.2217/PGS.15.93.
^ A US patent 4018895 A, Bryan B. Molloy & Klaus K. Schmiegel, "Aryloxyphenylpropylamines in treating depression", published 1977-04-19, assigned to Eli Lilly And Company
^ B1 US patent EP0052492 B1, Bennie Joe Foster & Edward Ralph Lavagnino, "3-aryloxy-3-phenylpropylamines", published 1984-02-29, assigned to Eli Lilly And Company
^ 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.
^ "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. Unipolar major depression in adults: Augmentation of antidepressants with stimulants and stimulant-like drugs

English Journal

Atomoxetine administration combined with intensive speech therapy for post-stroke aphasia: Evaluation using a novel SPECT method.

Yamada N1, Kakuda W, Yamamoto K, Momosaki R, Abo M.
The International journal of neuroscience.Int J Neurosci.2015 Aug 13:1-28. [Epub ahead of print]
OBJECTIVES: We clarified the safety, feasibility, and efficacy of atomoxetine administration combined with intensive speech therapy (ST) for patients with post-stroke aphasia. In addition, we investigated the effect of atomoxetine treatment on neural activity of surrounding lesioned brain areas.MATE
PMID 26268403

Effects of the CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites.

Byeon JY1, Kim YH, Na HS, Jang JH, Kim SH, Lee YJ, Bae JW, Kim IS, Jang CG, Chung MW, Lee SY.
Archives of pharmacal research.Arch Pharm Res.2015 Aug 9. [Epub ahead of print]
To investigate the effect of the variant CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites, 4-hydroxyatomoxetine (4-HAT) and N-desmethylatomoxetine (NAT), in healthy subjects, a single oral dose of atomoxetine was administered to 62 subjects with a CYP2D6*wt/*wt (*wt = *1
PMID 26254792

Attention Deficit Hyperactivity Disorder Medication Use Among Teens and Young Adults.

Johansen ME1, Matic K2, McAlearney AS3.
The Journal of adolescent health : official publication of the Society for Adolescent Medicine.J Adolesc Health.2015 Aug;57(2):192-7. doi: 10.1016/j.jadohealth.2015.04.009. Epub 2015 May 27.
PURPOSE: The purpose of this study was to determine rates of stimulant/atomoxetine use among teens (aged 12-17 years) and young adults (aged 18-23 years) and to investigate associations in medication use before and after the transition from teen to young adult.METHODS: Repeated cross-sectional analy
PMID 26026476

Related Pictures

File:Strattera atomoxetin.jpg - Wikimedia STRATTERA (ATOMOXETINE HYDROCHLORIDE) strattera in children dosing Strattera Pill Identifier Eli Lilly's Strattera Faces Generic

★リンクテーブル★

リンク元

「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 ;
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　　[★]

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

[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] "STRATTERA^® (atomoxetine hydrochloride) CAPSULES for Oral Use. Full Prescribing Information" (PDF). Indianapolis, USA: Eli Lilly and Company. 20 February 2014. Retrieved 23 May 2014.

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[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.

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[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.

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[PMID27518170-13] Todor, I; Popa, A; Neag, M; Muntean, D; Bocsan, C; Buzoianu, A; Vlase, L; Gheldiu, AM; Briciu, C (NaN). "Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers.". Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques. 19 (2): 198–207. PMID 27518170. Check date values in: |date= (help)

[PMID21765848-14] Kasi, PM; Mounzer, R; Gleeson, GH (2011). "Cardiovascular side effects of atomoxetine and its interactions with inhibitors of the cytochrome p450 system.". Case reports in medicine. 2011: 952584. PMID 21765848. doi:10.1155/2011/952584.

[PMID12412820-15] Belle, DJ; Ernest, CS; Sauer, JM; Smith, BP; Thomasson, HR; Witcher, JW (November 2002). "Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics.". Journal of clinical pharmacology. 42 (11): 1219–27. PMID 12412820.

[PMID19154426-16] Scherer, D; Hassel, D; Bloehs, R; Zitron, E; von Löwenstern, K; Seyler, C; Thomas, D; Konrad, F; Bürgers, HF; Seemann, G; Rottbauer, W; Katus, HA; Karle, CA; Scholz, EP (January 2009). "Selective noradrenaline reuptake inhibitor atomoxetine directly blocks hERG currents.". British journal of pharmacology. 156 (2): 226–36. PMID 19154426. doi:10.1111/j.1476-5381.2008.00018.x.

[PMID15910008-17] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r Sauer, JM; Ring, BJ; Witcher, JW (2005). "Clinical pharmacokinetics of atomoxetine.". Clinical pharmacokinetics. 44 (6): 571–90. PMID 15910008. doi:10.2165/00003088-200544060-00002.

[part2-18] "21-411 Strattera Clinical Pharmacology Biopharmaceutics Review Part 2" (PDF).

[NPP2002-19] 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.

[PMID20403082-20] Koda, K; Ago, Y; Cong, Y; Kita, Y; Takuma, K; Matsuda, T (July 2010). "Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice.". Journal of neurochemistry. 114 (1): 259–70. PMID 20403082. doi:10.1111/j.1471-4159.2010.06750.x.

[DingNaganawa2014-21] 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

[PMID20423340-22] 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.

[PMID28167075-23] Barygin, OI; Nagaeva, EI; Tikhonov, DB; Belinskaya, DA; Vanchakova, NP; Shestakova, NN (1 April 2017). "Inhibition of the NMDA and AMPA receptor channels by antidepressants and antipsychotics.". Brain research. 1660: 58–66. PMID 28167075. doi:10.1016/j.brainres.2017.01.028.

[24] Di Miceli, M; Gronier, B (June 2015). "Psychostimulants and atomoxetine alter the electrophysiological activity of prefrontal cortex neurons, interaction with catecholamine and glutamate NMDA receptors.". Psychopharmacology. 232 (12): 2191–205. PMID 25572531. doi:10.1007/s00213-014-3849-y.

[PMID24348020-25] Udvardi, PT; Föhr, KJ; Henes, C; Liebau, S; Dreyhaupt, J; Boeckers, TM; Ludolph, AG (2013). "Atomoxetine affects transcription/translation of the NMDA receptor and the norepinephrine transporter in the rat brain--an in vivo study.". Drug design, development and therapy. 7: 1433–46. PMID 24348020. doi:10.2147/DDDT.S50448.

[26] Maltezos, S; Horder, J; Coghlan, S; Skirrow, C; O'Gorman, R; Lavender, TJ; Mendez, MA; Mehta, M; Daly, E; Xenitidis, K; Paliokosta, E; Spain, D; Pitts, M; Asherson, P; Lythgoe, DJ; Barker, GJ; Murphy, DG (18 March 2014). "Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study.". Translational psychiatry. 4: e373. PMID 24643164. doi:10.1038/tp.2014.11.

[27] Chang, JP; Lane, HY; Tsai, GE (2014). "Attention deficit hyperactivity disorder and N-methyl-D-aspartate (NMDA) dysregulation.". Current pharmaceutical design. 20 (32): 5180–5. PMID 24410567.

[PMID20393461-28] Kobayashi, T; Washiyama, K; Ikeda, K (June 2010). "Inhibition of G-protein-activated inwardly rectifying K+ channels by the selective norepinephrine reuptake inhibitors atomoxetine and reboxetine.". Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 35 (7): 1560–9. PMID 20393461. doi:10.1038/npp.2010.27.

[PMID15225731-29] 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.

[PDSP-30] 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.

[31] 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.

[FDAPI-32] "Strattera Package Insert" (PDF). FDA.

[PMID26314574-33] Brown, JT; Bishop, JR (2015). "Atomoxetine pharmacogenetics: associations with pharmacokinetics, treatment response and tolerability.". Pharmacogenomics. 16 (13): 1513–20. PMID 26314574. doi:10.2217/PGS.15.93.

[34] A US patent 4018895 A, Bryan B. Molloy & Klaus K. Schmiegel, "Aryloxyphenylpropylamines in treating depression", published 1977-04-19, assigned to Eli Lilly And Company

[35] B1 US patent EP0052492 B1, Bennie Joe Foster & Edward Ralph Lavagnino, "3-aryloxy-3-phenylpropylamines", published 1984-02-29, assigned to Eli Lilly And Company

[36] 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.

[orangeBook-37] "Patent and Exclusivity Search Results". Electronic Orange Book. US Food and Drug Administration. Retrieved 26 April 2009.

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

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

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

[42] 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.

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[44] 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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Strattera