StartseiteMCPWorkbenchSkills
StartseiteWorkbenchBenachrichtigungenMein Bereich
Huagongshe Open Project：[email protected]KI-Anbindung: llms.txt · MCP-AnleitungDatenschutz · Nutzungsbedingungen · Supportv1.7.8
Zurück
HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
HCID 54841Erstellt: 3. November 2026

Atomoxetine

Tomoxetine · (R)-N-methyl-3-phenyl-3-(o-tolyloxy)propan-1-amine · (3R)-N-methyl-3-(2-methylphenoxy)-3-phenylpropan-1-amine · HSDB7352 · HSDB 7352 · HSDB-7352 · TomoxetineHcl · (r)-tomoxetine

https://huagongshe.com/de/chemical/54841

Molekülstruktur von Atomoxetine

Identifikatoren & physikalische Daten

CAS No.82248-59-7
SummenformelC17H21NO
Durchschnittliche Molmasse255,35 g/mol
Monoisotopische Masse255,16231429 g/mol
SMILESCNCC[C@@H](Oc1ccccc1C)c1ccccc1
InChIKeyVHGCDTVCOLNTBX-QGZVFWFLSA-N
PubChem CID54841
ChEMBLCHEMBL641
ChEBICHEBI:127342
EC No.617-427-9
DTXSIDDTXSID9044297

Chemische & physikalische Eigenschaften

XLogP3,7
Polarare Oberfläche (TPSA)21,3
H-Brücken-Donoren1
H-Brücken-Akzeptoren2
Frei drehbare Bindungen6
Schwere Atome19
Formalladung0
Komplexität237
ArzneimittelPharmaceuticals -> Listed in ZINC15
LogP (Verteilungskoeffizient)3.9
LöslichkeitWhite to practically white solid ... solubility of 27.8 mg/L in water. /Hydrochloride/3.90e-03 g/L
Human DrugsBreast FeedingLactationMilk, HumanAdrenergic Uptake Inhibitors
Siedepunkt64-65 ºC at 0.760 mmHg389.0±37.0 °C(Predicted)
Schmelzpunkt161-165 ºC
Physical DescriptionSolid
Dissociation Constants10.110.13
Collision Cross Section159.47 Ų [M+K]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]164.2 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)]
Dichte1.023±0.06 g/cm3(Predicted)
pKa (Säurekonstante)10.15±0.10(Predicted)
CAS Datenbank83015-26-3(CAS DataBase Reference)

Sicherheit & Vorschriften

GHS-EinstufungDangerH301+H331 (33.3%): Toxic if swallowed or if inhaled [Danger Acute toxicity, oralacute toxicity, inhalation]P203, P261, P264, P264+P265, P270, P271, P273, P280, P301+P316, P304+P340, P305+P354+P338, P316, P317, P318, P321, P330, P391, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 3 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
FDA-AnforderungenThe Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including atomoxetine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Atomoxetine hydrochloride/
Special ReportsBarton JAtomoxetine: A New Pharmacotherapeutic Approach in the Management of Attention Deficit/Hyperactivity DisorderArch Dis Child 90 (Suppl 1): i26-9 (2005)Kratochvil CJ et alAtomoxetine in the Treatment of Attention Deficit Hyperactivity DisorderExpert Rev Neurother 4 (4): 601-11 (2004)
Hazard Classes and CategoriesAcute Tox. 3 (100%)
LagerbedingungenStore at 25 °C (77 °F)excursions permitted to 15 to 30 °C (59 to 86 °F).
EntsorgungsverfahrenSRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
TreatmentAn airway should be established. Monitoring of cardiac and vital signs is recommended, along with appropriate symptomatic and supportive measures. Gastric lavage may be indicated if performed soon after ingestion. Activated charcoal may be useful in limiting absorption. Because atomoxetine is highly protein-bound, dialysis is not likely to be useful in the treatment of overdose. (L1712)

Anwendungen & Verwendung

Verwenden

(R)-Tomoxetine is a compound active at novel site on receptor-operated calcium channels useful for treatment of neurological disorders and diseases.

WechselwirkungenStrattera should be administered with caution to patients being treated with systemically-administered (oral or intravenous) albuterol (or other beta2 agonists) because the action of albuterol on the cardiovascular system can be potentiated resulting in increases in heart rate and blood pressure. Albuterol (600 mcg iv over 2 hours) induced increases in heart rate and blood pressure. These effects were potentiated by atomoxetine (60 mg BID for 5 days) and were most marked after the initial coadministration of albuterol and atomoxetine. However, these effects on heart rate and blood pressure were not seen in another study after the coadministration with inhaled dose of albuterol (200-800 ug) and atomoxetine (80 mg QD for 5 days) in 21 healthy Asian subjects who were excluded for poor metabolizer status.The manufacturer states that atomoxetine is contraindicated in patients currently receiving or having recently received (i.e., within 2 weeks) monoamine oxidase (MAO) inhibitor therapy. In addition, at least 2 weeks should elapse after discontinuing atomoxetine before initiating MAO inhibitor therapy. Severe, potentially fatal, reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma) have been reported in patients receiving other drugs that affect brain monoamine concentrations concomitantly with MAO inhibitor therapy.Potential pharmacokinetic interaction (decreased metabolism of atomoxetine) when atomoxetine is used concomitantly with drugs that inhibit the activity of the cytochrome P-450 2D6 (CYP2D6) isoenzyme. Inhibitors of CYP2D6 may increase plasma concentrations of atomoxetine in patients with the extensive-metabolizer phenotype to such an extent that plasma concentrations of the drug are similar to those achieved in poor metabolizers. When atomoxetine is used concomitantly with potent CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine), or in patients with poor-metabolizer phenotypes of the CYP2D6 isoenzyme, the manufacturer states that dosage adjustment of atomoxetine should be considered. However, in vitro studies suggest that concomitant use of atomoxetine with CYP2D6 inhibitors will not increase plasma concentrations of atomoxetine in patients with the poor-metabolizer phenotype.Potential pharmacologic interaction (increased hypertensive effects) with concomitant use of pressor agents (e.g., dopamine, dobutamine) and atomoxetine. Use with caution.For more Interactions (Complete) data for ATOMOXETINE (6 total), please visit the HSDB record page.
HepatotoxicityAtomoxetine has been linked to serum aminotransferase elevations in a small proportion of patients (~0.5%). More importantly, there have been several reports of clinically apparent acute liver injury due to atomoxetine. The onset of injury was within 3 to 12 weeks of starting the medication. The typical pattern of serum enzyme elevations was hepatocellular with marked increases in serum aminotransferase levels (often >20 times upper limit of normal) and clinical features that resembled acute viral hepatitis. Most cases have been self-limited, but instances of acute liver failure sometimes requiring emergency liver transplantation have been reported. Immunoallergic features were not found, but several patients with acute injury had antinuclear antibody and at least one patient had other features that resembled autoimmune hepatitis (with typical liver histology and high levels of immunoglobulins in serum).
Unerwünschte WirkungenAtomoxetine has a United States (US) boxed warning for suicidal ideation in children and adolescents. An analysis of multiple short-term trials revealed increased suicidal ideation in children and adolescents treated with atomoxetine (0.4%) compared to those treated with a placebo (0%). Children and adolescents who start on atomoxetine require close monitoring for suicidal ideation and unusual changes in behavior. Clinicians should always perform a risk-benefit analysis before starting anyone on atomoxetine.
ExpositionspfadeAtomoxetine is rapidly absorbed after oral administration, with absolute bioavailability of about 63% in EMs and 94% in PMs. Drugs that elevate gastric pH (magnesium hydroxide/aluminum hydroxide, omeprazole) have no effect on atomoxetine bioavailability. Absorption is minimally affected by food.
ToxizitätsübersichtIDENTIFICATION AND USE: Atomoxetine, as Strattera, is indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). HUMAN EXPOSURE AND TOXICITY: Atomoxetine increased the risk of suicidal ideation in short-term studies in children or adolescents with ADHD. Symptoms accompanying acute and chronic overdoses of atomoxetine include gastrointestinal symptoms, somnolence, dizziness, tremor, abnormal behavior, hyperactivity, agitation, and signs and symptoms consistent with mild to moderate sympathetic nervous system activation (e.g., tachycardia, blood pressure increased, mydriasis, dry mouth). Less commonly, there have been reports of QT prolongation and mental changes, including disorientation and hallucinations. Atomoxetine may cause clinically significant hepatotoxicity either by metabolic idiosyncrasy or by inducing autoimmune hepatitis. There have been fatalities reported involving a mixed ingestion overdose of Strattera and at least one other drug. Sudden deaths, stroke, and myocardial infarction have been reported in both children and adults with structural cardiac abnormalities or other serious heart problems. ANIMAL STUDIES: The median lethal oral dose of atomoxetine hydrochloride in animals was estimated to be 25 mg/kg for cats, >37.5 mg/kg for dogs, and 0.190 mg/kg in rats and mice. Premonitory signs of toxicity following single oral doses of atomoxetine in animals included mydriasis and reduced pupillary light reflex, mucoid stools, salivation, vomiting, ataxia, tremors, myoclonic jerking, and convulsions. Chronic toxicity studies of up to 1 year were conducted in adult rats and dogs. There was no major target organ toxicity observed in dogs given oral doses up to 16 mg/kg/day or in rats given atomoxetine in the diet at time-weighted average doses up to 47 mg/kg/day. These doses are 4-5 times the maximum recommended daily oral dose in adults. Mild hepatic effects, characterized by mottling and pallor of the liver, increased relative liver weights, hepatocellular vacuolation, and slightly increased serum ALT values, occurred in male rats given time weighted average doses >/= 14 mg/kg/day. No hepatic effects were observed in dogs. Clinical signs of mydriasis, reduced pupillary light reflex, emesis, and tremors were observed in dogs, and these effects were minimal in adult dogs given >/= 8 mg/kg/day. No evidence of drug-associated teratogenicity or retarded fetal development was produced in rabbits or rats administered atomoxetine hydrochloride throughout organogenesis at oral doses up to 100 mg/kg/day and 150 mg/kg/day (13 times the maximum recommended daily oral dose in adults). In a rat fertility study, decreased pup weight and survival was observed, predominantly during the first week postpartum following maternal dietary atomoxetine timeweighted average doses of 23 mg/kg/day or higher. Atomoxetine hydrochloride was negative in a battery of genotoxicity studies that included a reverse point mutation assay (Ames Test), an in vitro mouse lymphoma assay, a chromosomal aberration test in Chinese hamster ovary cells, an unscheduled DNA synthesis test in rat hepatocytes, and an in vivo micronucleus test in mice. However, there was a slight increase in the percentage of Chinese hamster ovary cells with diplochromosomes, suggesting endoreduplication (numerical aberration). Atomoxetine hydrochloride was not carcinogenic in rats and mice when given in the diet for 2 years at time-weighted average doses up to 47 and 458 mg/kg/day, respectively.* Exercise caution when prescribing atomoxetine with other medications metabolized via CYP2D6, as plasma concentrations can be significantly affected, leading to toxicity. Evidence regarding the toxicity of atomoxetine is limited, with much of the data coming from case studies of overdoses. Tachycardia, nausea, vomiting, and hypertension were among the most common symptoms of toxicity. Activated charcoal therapy and support of vital signs appear to be sufficient care during acute toxicity.The precise mechanism by which atomoxetine produces its therapeutic effects in Attention-Deficit/Hyperactivity Disorder (ADHD) is unknown, but is thought to be related to selective inhibition of the pre-synaptic norepinephrine transporter, as determined through in-vitro studies. Atomoxetine appears to have minimal affinity for other noradrenergic receptors or for other neurotransmitter transporters or receptors.
Signs and SymptomsThe most commonly reported symptoms accompanying acute and chronic overdoses are somnolence, agitation, hyperactivity, abnormal behavior, and gastrointestinal symptoms.
Human Toxicity Excerpts/SIGNS AND SYMPTOMS/ Postmarketing reports indicate that Strattera can cause severe liver injury. Although no evidence of liver injury was detected in clinical trials of about 6000 patients, there have been rare cases of clinically significant liver injury that were considered probably or possibly related to Straterra use in postmarketing experience. Rare cases of liver failure have also been reported, including a case that resulted in a liver transplant. Because of probable underreporting, it is impossible to provide an accurate estimate of the true incidence of these reactions. Reported cases of liver injury occurred within 120 days of initiation of atomoxetine in the majority of cases and some patients presented with markedly elevated liver enzymes [>20 X upper limit of normal (ULN)], and jaundice with significantly elevated bilirubin levels (>2 X ULN), followed by recovery upon atomoxetine discontinuation. In one patient, liver injury, manifested by elevated hepatic enzymes up to 40 X ULN and jaundice with bilirubin up to 12 X ULN, recurred upon rechallenge, and was followed by recovery upon drug discontinuation, providing evidence that Strattera likely caused the liver injury. Such reactions may occur several months after therapy is started, but laboratory abnormalities may continue to worsen for several weeks after drug is stopped. The patient described above recovered from his liver injury, and did not require a liver transplant./SIGNS AND SYMPTOMS/ Strattera (atomoxetine) increased the risk of suicidal ideation in short-term studies in children or adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD)./SIGNS AND SYMPTOMS/ There is limited clinical trial experience with Strattera overdose. During postmarketing, there have been fatalities reported involving a mixed ingestion overdose of Strattera and at least one other drug. There have been no reports of death involving overdose of Strattera alone, including intentional overdoses at amounts up to 1400 mg. In some cases of overdose involving Strattera, seizures have been reported. The most commonly reported symptoms accompanying acute and chronic overdoses of Strattera were gastrointestinal symptoms, somnolence, dizziness, tremor, and abnormal behavior. Hyperactivity and agitation have also been reported. Signs and symptoms consistent with mild to moderate sympathetic nervous system activation (e.g., tachycardia, blood pressure increased, mydriasis, dry mouth) have also been observed. Most events were mild to moderate. Less commonly, there have been reports of QT prolongation and mental changes, including disorientation and hallucinations./CASE REPORTS/ An eight-year-old female with attention deficient hyperactive disorder (ADHD) was treated with atomoxetine hydrochloride. She complained of increased abdominal pain and occasional emesisher transaminases and bilirubin were markedly elevated. She was admitted to a tertiary-care pediatric hospital and treated for drug-induced hepatitis. Atomoxetine was discontinued and supportive care was instituted. A liver biopsy showed hepatitis with moderate piecemeal necrosis. Clinical status and liver function tests improved over 13 days of hospitalization. ...For more Human Toxicity Excerpts (Complete) data for ATOMOXETINE (18 total), please visit the HSDB record page.
Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Drug Induced Liver InjuryDrug-Induced Liver Injury Severity and Toxicity (DILIst)atomoxetineDILI PositiveOralDOI:10.1016/j.drudis.2019.09.022
Non-Human Toxicity Excerpts/LABORATORY ANIMALS: Acute Exposure/ The median lethal oral dose of atomoxetine hydrochloride in animals was estimated to be 25 mg/kg for cats, >37.5 mg/kg for dogs, and >/= 190 mg/kg in rats and mice. Premonitory signs of toxicity following single oral doses of atomoxetine in animals included mydriasis and reduced pupillary light reflex, mucoid stools, salivation, vomiting, ataxia, tremors, myoclonic jerking, and convulsions./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Toxicity studies of up to 1 year were conducted in adult rats and dogs to evaluate the potential chronic toxicity of atomoxetine. There was no major target organ toxicity observed in dogs given oral doses up to 16 mg/kg/day or in rats given atomoxetine in the diet at time-weighted average doses up to 47 mg/kg/day. These doses are approximately 6-7 times the maximum recommended daily oral dose in children, and approximately 4-5 times the maximum recommended daily oral dose in adults, on a mg/sq m basis. Mild hepatic effects, characterized by mottling and pallor of the liver, increased relative liver weights, hepatocellular vacuolation, and slightly increased serum ALT values, occurred in male rats given timeweighted average doses > or = 14 mg/kg/day. No hepatic effects were observed in dogs. Clinical signs of mydriasis, reduced pupillary light reflex, emesis, and tremors were observed in dogs, and these effects were minimal in adult dogs given > or = 8 mg/kg/day. Similar clinical signs were observed in young dogs (8 weeks of age) given atomoxetine orally for 1 month./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Atomoxetine HCl was not carcinogenic in rats and mice when given in the diet for 2 years at time-weighted average doses up to 47 and 458 mg/kg/day, respectively. The highest dose used in rats is approximately 8 and 5 times the maximum human dose in children and adults, respectively, on a mg/sq m basis. Plasma levels (AUC) of atomoxetine at this dose in rats are estimated to be 1.8 times (extensive metabolizers) or 0.2 times (poor metabolizers) those in humans receiving the maximum human dose. The highest dose used in mice is approximately 39 and 26 times the maximum human dose in children and adults, respectively, on a mg/sq m basis./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ No evidence of drug-associated teratogenicity or retarded fetal development was produced in rabbits or rats administered atomoxetine hydrochloride throughout organogenesis at oral doses up to 100 mg/kg/day and 150 mg/kg/day (at least 20 times the maximum recommended daily oral dose in children and 13 times the maximum recommended daily oral dose in adults, on a mg/sq m basis). In a rat fertility study, decreased pup weight and survival was observed, predominantly during the first week postpartum following maternal dietary atomoxetine timeweighted average doses of 23 mg/kg/day or higher. No adverse effects were observed in surviving pups.For more Non-Human Toxicity Excerpts (Complete) data for ATOMOXETINE (19 total), please visit the HSDB record page.
Populations at Special Risk... A fraction of the population (about 7% of Caucasians and 2% of African-Americans) are poor metabolizers (PMs) of CYP2D6 drugs. These individuals have reduced activity in this pathway resulting in 10-fold higher AUCs, 5-fold higher peak plasma concentrations, and slower elimination (plasma half life of about 24 hours) of atomoxetine compared with those who have normal activity (extensive metabolizers (EMs)).The manufacturer also states that atomoxetine should not be used in patients with angle-closure glaucoma, since the drug was associated with an increased risk of mydriasis in some patients during controlled clinical trials.Seizures have been reported in the postmarketing period. The postmarketing seizure cases include patients with pre-existing seizure disorders and those with identified risk factors for seizures, as well as patients with neither a history of nor identified risk factors for seizures. The exact relationship between Strattera and seizures is difficult to evaluate due to uncertainty about the background risk of seizures in ADHD patients.Strattera should not be used in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate if they experience increases in blood pressure or heart rate that could be clinically important (for example, 15 to 20 mm Hg in blood pressure or 20 beats per minute in heart rate).For more Populations at Special Risk (Complete) data for ATOMOXETINE (7 total), please visit the HSDB record page.
Sicherheitshinweise (S)22-24/25
Gefahrstoffdaten83015-26-3(Hazardous Substances Data)