Atomoxetine Hydrochloride
ATOMOXETINE · ATOMOXETINE HCL · Strattera · ATOMOXITINE · Atomoxetine HCI · TOMOXETINE HYDROCHLORIDE · LY 139603 · LY 139603 HCl
Identifikatoren & physikalische Daten
| CAS No. | 82248-59-7 |
|---|---|
| Summenformel | C17H22ClNO |
| Durchschnittliche Molmasse | 291,8 g/mol |
| Monoisotopische Masse | 291,138992 g/mol |
| SMILES | CNCC[C@@H](Oc1ccccc1C)c1ccccc1.Cl |
| InChIKey | LUCXVPAZUDVVBT-UNTBIKODSA-N |
| PubChem CID | 54840 |
| ChEMBL | CHEMBL1702 |
| ChEBI | CHEBI:331697 |
| EC No. | 629-925-3 |
| DTXSID | DTXSID2044266 |
Chemische & physikalische Eigenschaften
| Polarare Oberfläche (TPSA) | 21,3 |
|---|---|
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 2 |
| Frei drehbare Bindungen | 6 |
| Schwere Atome | 20 |
| Formalladung | 0 |
| Komplexität | 237 |
| Human Drugs | FDA approved drugs -> Active ingredient |
| Collision Cross Section | 162.4 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| Schmelzpunkt | 167-169°C |
| Flammpunkt | 9℃ |
| Lagerbedingungen | 2-8°C |
| Löslichkeit | soluble in MethanolSoluble to 50 mM in water with gentle warming |
| Aggregatzustand | solid |
| pKa (Säurekonstante) | 10.13(at 25℃) |
| Farbe | White to Almost white |
| Merck | 14,863 |
| BCS Class | 1 |
| Hauptanwendungen | pharmaceutical (small molecule) |
| InChI | InChI=1/C17H21NO.ClH/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,12-13H2,1-2H31H/t17-/s3 |
| InChIKey | LUCXVPAZUDVVBT-UNTBIKODSA-N |
| SMILES | O([C@H](CCNC)C1C=CC=CC=1)C1=CC=CC=C1C.Cl |&1:1,r| |
| CAS Datenbank | 82248-59-7(CAS DataBase Reference) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH301 (70%): Toxic if swallowed [Danger Acute toxicity, oral]P203, P260, P261, P262, P264, P264+P265, P270, P271, P273, P280, P284, P301+P316, P301+P317, P302+P352, P304+P340, P305+P351+P338, P305+P354+P338, P316, P317, P318, P319, P320, P321, P330, P337+P317, P361+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 10 reports by companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Hazard Classes and Categories | Acute Tox. 3 (70%) |
| Treatment | An 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) |
| Expositionspfade | Atomoxetine 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. |
| Toxizitätsübersicht | 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 Symptoms | The most commonly reported symptoms accompanying acute and chronic overdoses are somnolence, agitation, hyperactivity, abnormal behavior, and gastrointestinal symptoms. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)Atomoxetine hydrochloridevMost-DILI-concern |
Anwendungen & Verwendung
Beschreibung
Atomoxetine is the first non-stimulant marketed for the treatment of attention deficit hyperactivity disorder (ADHD). It is the R-stereoisomer of the racemate tomoxetine and is a selective and potent norepinephrine uptake inhibitor (Ki=0.7–1.9 nM) that is devoid of binding to monoamine receptor. It also has little effect on dopamine and serotonin reuptake or acetylcholine, H1 histamine, alpha1 or alpha1-adrenergic or dopamine receptors. It is prepared from racemic 1-phenylbut-3-en-1-ol via a selective enzymatic acylation leaving the desired S-stereoisomer as the alcohol. This alcohol is converted via a Mitsunobu reaction with ortho-cresol to the corresponding ether with isomeric R-configuration. Ozonolysis and reduction steps provided the terminal alcohol that is mesylated and displaced with methylamine. Its selectivity for norepinephrine relative to dopamine inhibition was demonstrated in vivo preclinically. In a two-lever (two condition) discriminative stimulus effect study in squirrel monkeys, tomoxetine and other norepinephrine uptake inhibitors substituted for cocaine under low-dose training conditions, whereas dopamine uptake inhibitors substituted for cocaine in both low and high-dose conditions. In clinical ADHD studies in adolescents, it was significantly different from placebo in 1.2 and 1.8 mpk/day dosing. In the clinical study in adults using the CAARS scale a 95 mg/day dose provided greater than 30% improvement in total scores. Atomoxetine is about 63% orally bioavailable, is highly protein bound (98%, primarily to albumin) and has a half-life of about 5.2 h. It is metabolized by CYP2D6 resulting in differential clearance for poor metabolizers (halflife of 19 h with a 10 times higher AUC) relative to extensive metabolizers. The total daily dose for children, adolescents and adults is a maximum of 100 mg/day. Common side effects in children and adults include nausea, decreased appetite, and dizziness. Adults may also have insomnia.
Verwenden
Atomoxetine hydrochloride, a Norepinephrine reuptake inhibitor, is used as a Psychotherapeutic and anti-depressant. These Secondary Standards are qualified as Certified Reference Materials. These are suitable for use in several analytical applications, including but not limited to pharma release testing, pharma method development for qualitative and quantitative analyses, food and beverage quality control testing, and other calibration requirements. Atomoxetine hydrochloride may be used as a pharmaceutical reference standard for determining atomoxetine hydrochloride in pharmaceutical formulations by spectrophotometric method.