Buspirone, mirtazapine, saquinavir, and verapamil were purchased from Sigma (St. Louis, MO, USA). Midazolam, 1’-hydroxyl-midazolam, nomifensine, and dextromethorphan were purchased from National Institutes for Food and Drug Control (Beijing, China). Amodiaquine and N-desethyl amodiaquine were purchased from Toronto Research Chemical Inc. (North York, ON, Canada). β-nicotinamide adenine dinucleotide 2′-phosphate reduced tetrasodium salt (NADPH) was purchased from Beijing Dingguochangsheng Biotechnology Co., LTD (Beijing, China). All solvents (acetonitrile, methanol, and water) were of high-performance liquid chromatography grade and purchased from Fisher Scientific (Pittsburgh, PA, USA). Pooled HLM was obtained from BD Biosciences (Woburn, MA, USA).
Mirtazapine
Manufactured by Merck Group
Sourced in United States
Mirtazapine is a laboratory equipment product manufactured by the Merck Group. It is a drug used in the analysis and research of various chemical compounds and biological samples. Mirtazapine is primarily used as a reference standard or internal standard in analytical procedures.
Automatically generated - may contain errors
Lab products found in correlation
Buspirone, by Merck Group (1 mentions)
Saquinavir, by Merck Group (1 mentions)
Acetonitrile, by Thermo Fisher Scientific (1 mentions)
Methanol, by Thermo Fisher Scientific (1 mentions)
Verapamil, by Merck Group (1 mentions)
Pooled hlm, by BD (1 mentions)
Bupropion hydrochloride, by Merck Group (1 mentions)
Amitriptyline hydrochloride, by Merck Group (1 mentions)
Maprotiline hydrochloride, by Merck Group (1 mentions)
Ivermectin, by Merck Group (1 mentions)
4 chloro dl phenylalanine methyl ester hydrochloride, by Merck Group (1 mentions)
Adenosine 5 diphosphate sodium salt, by Merck Group (1 mentions)
Adenosine 5 triphosphate disodium salt, by Merck Group (1 mentions)
2 3 o 4 benzoylbenzoyl adenosine 5 triphosphate triethylammonium salt, by Merck Group (1 mentions)
N 2 chloroethyl n ethyl 2 bromobenzylamine dsp 4, by Merck Group (1 mentions)
Fura 2 am, by Dojindo Laboratories (1 mentions)
Amitriptyline, by Merck Group (1 mentions)
Escitalopram, by Merck Group (1 mentions)
Agomelatine, by Merck Group (1 mentions)
Imipramine, by Merck Group (1 mentions)
10 protocols using mirtazapine
1
High-Throughput Metabolic Profiling Assay
2
Screening of Approved Drugs for Neuroprotection
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Reagents were obtained from the following sources: adenosine 5’-triphosphate disodium salt (ATP), 2’(3’)-O-(4-Benzoylbenzoyl)adenosine 5’-triphosphate triethylammonium salt (BzATP), adenosine 5'-diphosphate sodium salt (ADP), amitriptyline hydrochloride, bupropion hydrochloride, clomipramine hydrobromide, maprotiline hydrochloride, mirtazapine, ivermectin, 4-Chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) from Sigma-Aldrich (St. Louis, MO, USA); Fura-2-AM from Dojindo (Kumamoto, Japan); duloxetine hydrochloride and paroxetine hydrochloride from Toronto Research Chemicals (Toronto, Canada); pyridoxal phosphate-6-azophenyl-2’,4’-disulphonic acid (PPADS) tetrasodium salt from Tocris Bioscience (Bristol, UK). The approved drugs library of 1979 compounds were provided in the form of 96-well plate format by Drug Discovery Initiative, DDI, The University of Tokyo (Tokyo, Japan).
3
Biotransformation of Structurally Similar Compounds
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The
ten selected MPs are from three structurally
similar groups: phenylureas, tertiary amides, and tertiary amines
(Table S1). They include the four compounds (i.e., isoproturon, valsartan,
venlafaxine, and ranitidine) whose biotransformation rates were found
to associate positively with ammonia oxidation activity of activated
sludge communities or archael amoA transcript abundances.15 (link) Another six compounds were selected based on
structural similarity with the previous four compounds, and other
criteria including (1) minimal number of readily biotransformed functional
groups other than the three focused ones and (2) widely used pesticides
and pharmaceuticals with reference standards available. The ten parent
compounds, and literature-reported TPs (Table S1) of mianserin (MIA)
and ranitidine (RAN), as well as the analogue compounds used for analyzing
the structure of the major MIA TP (i.e., mirtazapine, analogue of
MIA; 1-oxo mirtazapine, and 10-oxo mirtazapine, analogues of the major
MIA TP) were purchased from Sigma-Aldrich Chemie GmbH (Buchs, Switzerland),
Dr. Ehrenstorfer GmbH (Augsburg, Germany), and Toronto Research Chemicals
(Toronto, Canada). Stock solutions of each reference compound were
prepared in methanol or ethanol (1 g/L), and stored at −20
°C until use.
ten selected MPs are from three structurally
similar groups: phenylureas, tertiary amides, and tertiary amines
(Table S1). They include the four compounds (i.e., isoproturon, valsartan,
venlafaxine, and ranitidine) whose biotransformation rates were found
to associate positively with ammonia oxidation activity of activated
sludge communities or archael amoA transcript abundances.15 (link) Another six compounds were selected based on
structural similarity with the previous four compounds, and other
criteria including (1) minimal number of readily biotransformed functional
groups other than the three focused ones and (2) widely used pesticides
and pharmaceuticals with reference standards available. The ten parent
compounds, and literature-reported TPs (Table S1) of mianserin (MIA)
and ranitidine (RAN), as well as the analogue compounds used for analyzing
the structure of the major MIA TP (i.e., mirtazapine, analogue of
MIA; 1-oxo mirtazapine, and 10-oxo mirtazapine, analogues of the major
MIA TP) were purchased from Sigma-Aldrich Chemie GmbH (Buchs, Switzerland),
Dr. Ehrenstorfer GmbH (Augsburg, Germany), and Toronto Research Chemicals
(Toronto, Canada). Stock solutions of each reference compound were
prepared in methanol or ethanol (1 g/L), and stored at −20
°C until use.
4
Evaluating Antidepressant Effects on Glioblastoma Cell Line
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The human glioblastoma multiforme cell line, T98G (Sigma-Aldrich, St. Louis, Missouri), was utilized for this study. Cell culture media, gentamicin, and fetal bovine serum were purchased from Gibco-BRL (Waltham, Massachusetts). Antidepressant drugs (imipramine, amitriptyline, fluoxetine, escitalopram, agomelatine, and mirtazapine) were obtained from Sigma-Aldrich (Saint Louis, Missouri). Plastics for cell cultures (monolayer and spheres) were purchased from Nunc (Waltham, Massachusetts), Falcon (Lexington, Tennessee), and Eppendorf (Hamburg, Germany).
5
Intraperitoneally Administered Mirtazapine
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Mirtazapine (16 mg/kg or 4 mg/kg, Sigma-Aldrich) was dissolved in DMSO and diluted to the appropriate dose with 1% Tween 80, immediately before use (the maximal final DMSO concentration was 2%). Tested compounds were dissolved with 1% Tween 80. Solutions of Mirtazapine and the tested compounds were administered intraperitoneally (ip) 30 min prior to the experiment. The control animals were given ip injections of the 2% DMSO in 1% Tween 80 (vehicle). The volume of vehicle or drug solutions was 10 mL/kg.
6
MPTP-Induced Parkinson's Model: Mirtazapine and Receptor Modulators
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Mice were injected with 20 mg/kg of MPTP (Sigma-Aldrich, St. Louis, MO, USA) or saline intraperitoneally (i.p.) every 2 hr for a total of four injections, resulting in a cumulative dose of 80 mg/kg, as described previously [51 (link)]. Mirtazapine (generously provided by Meiji Seika Pharma Co., Ltd., Japan) was dissolved in 0.5% carboxymethylcellulose, and was applied once a day with 4 or 16 mg/kg i.p. started from 1 hr after the final MPTP treatment for 4 days. WAY100635 (0.5 mg/kg, Sigma-Aldrich, St. Louis, MO, USA), prazosin (0.03 mg/kg, Sigma-Aldrich, St. Louis, MO, USA) and clonidine (0.15 mg/kg, Sigma-Aldrich, St. Louis, MO, USA) were dissolved in saline, and each of them was administered 1 hr before treating with Mirtazapine.
7
Oral Dosage of Agmatine and Mirtazapine
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Agmatine and mirtazapine were obtained from Sigma chemicals, Co. St. Louis. USA and were administered orally by stainless steel oral gavage. The selected dose of Agmatine was (100 mg/Kg) and mirtazapine was (30 mg/Kg) per day. Both drugs were dissolved in distilled water at the ratio of 1:1 w/v. Control groups received 0.9% saline.
8
Mirtazapine and WAY-100635 intracerebral infusion
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Mirtazapine (Merck & Co, Inc., Whitehouse Station, NJ, USA) was suspended in 0.15% tartaric acid, and the selective 5-HT 1A antagonist, WAY-100635 maleate (Sigma-Aldrich, MO, USA) was dissolved in 0.9% saline. Based on our own (An et al., 2013) and others' (Dos Santos et al., 2008) studies, the doses of Mirtazapine were chosen to be 0.15 or 1.5 μg/site, while the dose of WAY-100635 was chosen to be 0.925 μg/site. The vehicle alone was infused as a control.
9
Mirtazapine Infusion Effects in Rats
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Bilateral or unilateral infusions of Mirtazapine were given with a 33-gauge injector cannula connected by polyethylene tubing to motor-driven microsyringes. Mirtazapine (obtained from Merck & Co. Inc., Whitehouse Station, NJ, U.S.A.) was dissolved at a concentration of 6 µg/µl in 0.15% tartaric acid, and 0.5 µl was infused through each injector at a rate of 0.5 µl/min. The vehicle alone was administered as a control.
The doses of Mirtazapine were determined based on our previous experiments in which 3 μg of Mirtazapine into the MRN showed the anxiolytic-like effect (An et al., 2013) . The concentrations of lithium carbonate in the rat chow were chosen based on our previous studies, in which we observed that plasma lithium levels were 0.71±0.05 mEq/l after 7 days of 0.2% Li2CO3 treatment in diet (Muraki et al., 1999) . This plasma lithium level is within the clinical therapeutic range (0.5-1.2 mEq/l) (Suppes et al., 2008; Bauer et al., 2010) .
The doses of Mirtazapine were determined based on our previous experiments in which 3 μg of Mirtazapine into the MRN showed the anxiolytic-like effect (An et al., 2013) . The concentrations of lithium carbonate in the rat chow were chosen based on our previous studies, in which we observed that plasma lithium levels were 0.71±0.05 mEq/l after 7 days of 0.2% Li2CO3 treatment in diet (Muraki et al., 1999) . This plasma lithium level is within the clinical therapeutic range (0.5-1.2 mEq/l) (Suppes et al., 2008; Bauer et al., 2010) .
10
Citalopram, mirtazapine, and atipamezole effects
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Citalopram hydrobromide (a gift from Dainippon Sumitomo Pharma Co, Ltd, Osaka, Japan) was dissolved in 0.9% sterile saline. Atipamezole (Antisedan® 5 mg/mL; Orion Pharma, Espoo, Finland) was diluted with distilled water. Mirtazapine (obtained from Merck and Co, Inc, Whitehouse Station, NJ, USA) was dissolved in 0.15% tartaric acid. The vehicle alone was administered as a control. Citalopram was administered 60 minutes before testing, and Mirtazapine or atipamezole was administered 30 minutes before testing. Citalopram and atipamezole were injected subcutaneously at a volume of 1 mL/kg. Mirtazapine was injected intraperitoneally in a volume of 2 mL/kg. The doses and routes of administration of citalopram, Mirtazapine, and atipamezole used in this study were determined based on our previous experiments11 (link),12 (link) and on earlier reports by other investigators.14 (link),15 (link)
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