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Atomoxetine hydrochloride

Manufactured by Merck Group
Sourced in United States

Atomoxetine hydrochloride is a chemical compound used as a raw material in the production of various pharmaceutical products. It is a white or almost white, crystalline powder that is soluble in water and other organic solvents. The compound is primarily used as an intermediate in the synthesis of other active pharmaceutical ingredients and does not have a standalone function.

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6 protocols using atomoxetine hydrochloride

1

Analytical Method for Psychoactive Drugs

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Atomoxetine hydrochloride, desipramine hydrochloride, escitalopram oxalate, mianserine hydrochloride, n-hexane and dimethyl sulfoxide (DMSO) were purchased from Sigma Aldrich Chemie (Steinheim, Germany). Water HiPerSolv CHROMANORM for HPLC and acetonitrile HiPerSolv CHROMANORM for HPLC Gradient Grade, iso-amyl alcohol, potassium dihydrogen phosphate ultrapure and hydrochloric acid (HCl) 36.5-38.0% were purchased from VWR International (Darmstadt, Germany), and sodium hydroxide (NaOH) for analysis was from Merck (Darmstadt, Germany). Blank human blood was collected from healthy, drug-free voluntary blood donors and checked on bio-safety by the university hospital department of Transfusion Medicine. Plasma was obtained by centrifugation of blood treated with sodium heparin as anticoagulant. Pooled plasma was prepared and stored at -80°C until needed.
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2

Pharmacological Interventions in Animal Study

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Dextroamphetamine hemisulfate, atomoxetine hydrochloride, and SCH-23390 (R(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride) were purchased from Sigma-Aldrich (St. Louis, MO). Propofol was obtained from APP Pharmaceuticals (Shaumburg, IL). All drugs (except for the inhaled anesthetic sevoflurane) were administered intravenously via a lateral tail vein catheter. Drug solutions were freshly prepared each day by weighing and dissolving the drug in 1.0 ml of sterile normal saline before administration. The intravenous catheter and attached tubing (approximate total volume 2.0 ml) were always flushed with 3.0 ml of normal saline after drug administration to ensure complete drug delivery.
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3

Pharmacological Modulation of Monoaminergic Systems

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Ketamine and xylazine were obtained from Midwest Veterinary Supply (Lakeville, MN). Meloxicam was obtained from Norbrook Laboratories (Overland Park, KS). Atomoxetine hydrochloride (1044469) and fluoxetine hydrochloride (F132) were obtained from Sigma-Aldrich (St. Louis, MO). Citalopram hydrobromide (1427), reboxetine mesylate (1982), N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4,2958), prazosin hydrochloride (0623), (S)-duloxetine hydrochloride (4798), propranolol hydrochloride (0624), and (R)-(−)-phenylephrine hydrochloride (2838) were obtained from Tocris Biosciences (Minneapolis, MN). Fluoxetine, citalopram, prazosin, and reboxetine were dissolved in 1% DMSO. DSP-4, phenylephrine, atomoxetine, propranolol, and duloxetine were dissolved in saline (0.9% NaCl).
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4

Spectrophotometric Determination of Atomoxetine

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Analytical reagents were all employed without further purification. Mash Premiere for Pharmaceutical Industries (Badr city, Egypt) provided pharmaceutical grade atomoxetine hydrochloride and p-chloranil (Sigma Chemical Co., USA) 200 mg of p-chloranil were dissolved in a 100 mL volumetric flask with acetonitrile as the solvent to create 0.2% w/v. 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) (Sigma Chemical Co., USA) 0.3% w/v is produced by combining 300 mg of DDQ with acetonitrile and dissolving it in a 100 mL standard flask. El Nasr Chemical Co. provided the ethanol, methanol, acetonitrile, 1,4-dioxane, and dimethylformamide that were purchased (Abu Zaabal, Egypt).
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5

Neuroblastoma and Glioblastoma Cell Culture

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Human neuroblastoma cell line SH-SY5Y and human glioblastoma cell line U-87 MG were purchased from the American Type Culture Collection (Rockville, MD, USA). Cells were maintained in Dulbecco’s Modified Eagle’s Medium (Welgene; Seoul, Korea) supplemented with 10% fetal bovine serum (Welgene), 100 U/mL penicillin, and 0.1 mg/mL streptomycin (Welgene) in 95% air and 5% CO2 at 37°C. Cells were seeded at a density of 2×106/mL in 6-well plates or 150 mm dishes. The next day, cell media was changed to serum-free media and cells were treated with different concentration of atomoxetine hydrochloride or fluoxetine hydrochloride (Sigma-Aldrich; St. Louis, MO, USA) dissolved in dimethyl sulfoxide (DMSO). STO-609, a CaMKKα and CaMKKβ inhibitor [26 (link)], was purchased from Tocris (Ellisville, MO, USA) was prepared in DMSO and 2.5 μg/mL concentration administered 30 min before atomoxetine and fluoxetine treatments.
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6

Pharmacological Modulation of Cognitive Control

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Animals received each drug/dose in a random order to protect against order effects, with at least 3 days between treatment days to allow for sufficient washout. Atomoxetine hydrochloride was obtained from Sigma (Y0001586) and was dissolved in 0.9% NaCl (saline) which was administered via intraperitoneal injection at a dose of either 5 mg/kg or 10 mg/kg 30 min prior to the start of the Go/NoGo test. D-amphetamine hemisulfate was obtained from Sigma (A5880 and was dissolved in 0.9% NaCl (saline) which was administered via intraperitoneal injection at a dose of either 1 mg/kg or 2.5 mg/kg 10 min prior to the start of the Go/NoGo test22 (link),54 (link)). Additionally, a HcrtR1 antagonist was obtained from Boehringer Ingelheim (patent WO2017/178339) and was dissolved in 0.5% hydroxyethylcellulose (Sigma, 525944) and 0.015% Tween 80 (Sigma, P1754) in water which was administered via oral gavage at a dose of either 2.5 mg/kg, 7.5 mg/kg, or 12.5 mg/kg. In addition to the 7 drug/dose groups, two control groups were included in which mice received either an intraperitoneal injection of saline 10 min prior to the start of the Go/NoGo test or received the vehicle solution used to administer the HcrtR1 compound via oral gavage 60 min prior to the start of the Go/NoGo test.
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