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Atomoxetine, sold under the brand name Strattera among others, is a norepinephrine (noradrenaline) reuptake inhibitor which is approved for the treatment of attention deficit hyperactivity disorder (ADHD).
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
6.2.1 Pharmacogenomics
7 Chemistry
7.1 Synthesis
7.2 Detection in biological fluids
8 History
9 Society and culture
9.1 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.
The initial therapeutic effects of atomoxetine usually take 2–4 weeks to become apparent.
Unlike α 2 adrenoceptor agonists such as guanfacine and clonidine, atomoxetine’s use can be abruptly stopped without significant discontinuation effects being seen.
Contraindications include:
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
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:
Very common (>10% incidence) adverse effects include:
Nausea (26%)
Xerostomia (Dry mouth) (20%)
Appetite loss (16%)
Insomnia (15%)
Fatigue (10%)
Vomiting (in children and adolescents)
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%)
Sinus headache
Mood swings
Uncommon (0.1–1% incidence) adverse effects include:
Suicide-related events
Emotional lability
Syncope (fainting)
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
Liver injury
Acute liver failure
Urinary retention
Male genital pain
The FDA of the US has issued a black box warning for suicidal behaviour/ideation.
Atomoxetine is relatively non-toxic in overdose. Single-drug overdoses involving over 1500 mg of atomoxetine have not resulted in death.
Gastrointestinal symptoms
Abnormal behaviour
Dry mouth
Less common symptoms:
QTc interval prolongation
The recommended treatment for atomoxetine overdose includes use of activated charcoal to prevent further absorption of the drug.
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.
Atomoxetine has been found to directly inhibit hERG potassium currents with an IC 50 of 6.3 μM, which has the potential to cause arrhythmia.
Other notable drug interactions include:
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 α 1 adrenoceptor agonists, including pressors such as dobutamine or isoprenaline and β 2 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
Atomoxetine (and metabolites)
5-HT 1A
5-HT 1B
5-HT 1D
5-HT 2
5-HT 6
5-HT 7
α 1
α 2A
β 1
M 1
M 2
D 1
D 2
H 1
σ 1
3,470 a
K ir 3.1/3.2
10,900 b
K ir 3.2
12,400 b
K ir 3.1/3.4
6,500 b
Values are K i (nM). The smaller the value, the more strongly the drug binds to the site. All values are for human receptors unless otherwise specified. a rat cortex. b Xenopus oocytes. Additional sources:
Atomoxetine inhibits the presynaptic norepinephrine transporter (NET), 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 (DAT) expression is minimal.
Atomoxetine’s status as a serotonin transporter (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 NET and SERT, respectively.
Atomoxetine has been found to act as an NMDA receptor antagonist in rat cortical neurons at therapeutic concentrations.
Atomoxetine also reversibly inhibits GIRK currents in Xenopus oocytes in a concentration-dependent, voltage-independent, and time-independent manner. 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. It is not known whether this contributes to the therapeutic effects of atomoxetine in ADHD.
Orally administered atomoxetine is rapidly and completely absorbed.
Atomoxetine has a volume of distribution of 0.85 L/kg, with limited partitioning into red blood cells.
The half-life of atomoxetine varies widely between individuals, with an average range of 4.5 to 19 hours.
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.
Atomoxetine is excreted unchanged in urine at 96% and 80% of a total dose being excreted in urine, respectively.
Major metabolites of atomoxetine in humans.
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.
Japanese men homozygous for CYP2D6*10 have similarly been found to experience two-fold higher AUCs compared to extensive metabolizers.
Atomoxetine, or (−)-methyl[(3 R )-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
Original synthesis of atomoxetine, as patented by Eli Lilly and Company
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.
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.
Society and culture
Brand names
In India, atomoxetine is sold under brand names including AXETRA, Axepta, Attera, Tomoxetin, and Attentin. In Australia and Romania, atomoxetine is sold under the brand name Strattera. In Iran, atomoxetine is sold under brand names including Stramox.
There has been some suggestion that atomoxetine might be a helpful adjunct in people with major depression, particularly in cases with concomitant ADHD.
See also
Fluoxetine (4- trifluoromethyl instead of 2-methyl)

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