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64 protocols using imipramine hydrochloride

1

Synthesis and Characterization of DSP-1053

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DSP-1053 (6-(2-{4-[4-Bromo-3-(2-methoxyethoxy)benzyl]piperidin-1-yl}ethyl)-2,3-dihydro-4H-chromen-4-one benzenesulfonate) (Fig.1) and paroxetine hydrochloride (paroxetine) were synthesized in our laboratories. The rout of synthesis of DSP-1053 has been described previously (Nishida et al. 2012 ). Clomipramine hydrochloride (clomipramine), serotonin hydrochloride (5-HT), dopamine hydrochloride (dopamine), imipramine hydrochloride (imipramine), WAY-100635, pindolol, and R-(+)-8-hydroxy-DPAT (8-OH-DPAT) were purchased from Sigma Aldrich Japan (Tokyo, Japan). All radioligands were purchased from Perkin Elmer Japan (Kanagawa, Japan). For oral (p.o.) administration in rodent models, DSP-1053 and paroxetine were dissolved in 0.5% methylcellulose. In the S. murinus model, DSP-1053 and paroxetine were dissolved in 40% polyethylene glycol. Dosing volume was determined based on each animal body weight measured in the morning of each administration day (5 mL kg−1). Cell membranes expressing human serotonin transporter and 5-HT1A receptor were purchased from Perkin Elmer Japan. Chinese hamster ovary cells expressing human serotonin transporter used for [3H]5-HT uptake assay were established in our Pharmacology Research Laboratories at Sumitomo Dainippon Pharma Co., Ltd.
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2

Astaxanthin and Antidepressant Effects

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Trans-astaxanthin, imipramine hydrochloride, p-chlorophenylalanine HCl (PCPA, an inhibitor of serotonin synthesis), apomorphine hydrochloride, kynuramine dihydrobromide, 4-hydroxyquinoline, clorgyline, deprenyl, 5-hydroxytryptamine, noradrenaline, dopamine, 5-hydroxyindoleacetic acid (5-HIAA) and 4-dihydroxyphenylacetic acid (DOPAC) were purchased from Sigma Chemical Co. (USA). Moclobemide hydrochloride and sodium carboxymethyl cellulose were provided by Beijing Institute of Pharmacology and Toxicology (China). For oral administration (via gavage, i.g.), Trans-astaxanthin was dissolved in 0.5% sodium carboxymethyl cellulose and moclobemide was dissolved in redistilled water. For intraperitoneal injection, imipramine and fluoxetine were dissolved in redistilled water. In acute experiments, the behavioral and neurochemical tests were conducted 1 h after Trans-astaxanthin (20, 40, 80 mg/kg, i.g.) treatment [37 (link)]. The effects of positive antidepressants such as moclobemide (20 mg/kg, i.g.), imipramine (10 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) were tested 1 h (meclobemide) and 30 min (imipramine and fluoxetine) respectively, after administration of the drugs as previously described [20 (link), 38 ].
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3

Pharmacological Compounds Procurement Protocol

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Sertraline hydrochloride, U0126, and SB202190 were purchased from Wako Pure Chemicals Industries (Osaka, Japan). Fluoxetine hydrochloride was purchased from LKT Labs (St. Paul, MN, United States). Imipramine hydrochloride and mianserin hydrochloride were purchased from Sigma–Aldrich. Fluvoxamine maleate and SP600125 were purchased from Tokyo Chemical Industries (Tokyo, Japan). Other common laboratory reagents were also obtained from commercial sources.
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4

Repeated Antidepressant and Antiparkinsonian Drug Administration

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Drugs or physiological saline were injected repeatedly for 2 weeks. Imipramine hydrochloride (Sigma, Aldrich) was dissolved in redistilled water and administered at a dose of 10 mg/kg ip, once a day. Pramipexole dihydrochloride (Abcam Ascent) was dissolved in physiological saline and administered at a dose of 1 mg/kg sc twice a day, except for the last day when it was injected only once. The first drug injection was performed one day after the operation. Control animals received physiological saline instead of drugs.
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5

Receptor Binding Assay Protocol

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[3H]imipramine hydrochloride (47.5 Ci/mmol) was obtained from PerkinElmer Life Sciences Products, Inc. (Boston, MA) and stored at −20°C. (±)-Citalopram hydrobromide was purchased from MedChemExpress USA (New Jersey, USA). (±)-Epibatidine hydrochloride and QX-314 were obtained from Tocris Bioscience (Ellisville, MO, USA). Fluo-4 was obtained from Molecular Probes (Eugene, Oregon, USA). Euthasol (sodium pentobarbital, 100 mg/kg; sodium phenytoin, 12.82 mg/kg) was obtained from LeVet Pharma (Oudewater, Netherlands). Polyethylenimine, acetylcholine (ACh), probenecid, atropine, imipramine hydrochloride, and bovine serum albumin (BSA), were purchased from Sigma Chemical Co. (St. Louis, MO, USA). Salts were of analytical grade.
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6

Pharmacological Effects on Behavior

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Amphetamine, (+)-α-Methylphenethylamine hemisulfate, chlorpromazine hydrochloride, imipramine hydrochloride and scopolamine hydrobromide were purchased from Sigma (France). All those pharmacological compounds were dissolved in NaCl 0.9% as the vehicle were administered IP 30 min before tests, except scopolamine which was subcutaneously administered 20 min before spontaneous alternation test.
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7

Pharmacological Interventions in Behavioral Assays

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Traxoprodil (5, 10, 20, and 40 mg/kg, Sigma-Aldrich) was suspended in a 1 % aqueous solution of Tween 80 (POCH), whereas imipramine hydrochloride (15 and 30 mg/kg, Sigma-Aldrich), fluoxetine hydrochloride (5 mg/kg, Sigma-Aldrich), escitalopram oxalate (2 mg/kg, Sigma-Aldrich), reboxetine mesylate (2.5 mg/kg, Abcam Biochemicals), WAY 100,635 (0.1 mg/kg, Sigma-Aldrich), and ritanserin (4 mg/kg, Sigma-Aldrich) were dissolved in physiological saline (0.9 % NaCl). The solutions/suspension were prepared immediately prior to the experiments and were administered intraperitoneally (i.p.) 60 min before testing. The doses and pretreatment schedules were selected on the basis of the literature data and the results of our previous experiments (Poleszak et al. 2005 (link), 2007a (link), 2011 (link), 2013 (link); Szewczyk et al. 2002 (link), 2009 (link)). Animals from the control groups received i.p. injections of the vehicle (saline). The volume of all administered solutions/suspension was 10 ml/kg.
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8

Antidepressant Effects on Stress-Induced Diabetes

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Imipramine hydrochloride and fluoxetine hydrochloride powders (Sigma-Aldrich chemicals Co., Germany) were dissolved in saline and administered i.p. in a volume of 2 ml/kg. Ninety-two rats were divided into 2 main groups. The first group (non-diabetic rats) was subdivided into 4 subgroups: Naïve group (n = 10); not exposed to CRS, CRS vehicle-treated group (n = 11); exposed to CRS for 6 weeks and received vehicle i.p., CRS FLU-treated group (n = 14); received fluoxetine 10mg/Kg/day i.p. [19 (link)] and CRS IMIP-treated group (n = 14); received imipramine 10mg/Kg/day i.p [20 (link)]. The second group (diabetic rats) fed HFD for 2 weeks followed by STZ 35 mg/kg, i.p) and was subdivided into 4 subgroups: Control DM group (n = 10); not exposed to CRS, DM/CRS vehicle-treated group (n = 9); exposed to CRS for 6 weeks and received vehicle i.p., DM/CRS FLU-treated group (n = 12); received fluoxetine and DM/CRS IMIP-treated group (n = 14); received imipramine. All treatments were received following the daily stress regimen for the last 3 weeks of CRS.
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9

Pharmacological Interventions in Behavioral Tests

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Compound 17 (25, 50, 75 mg/kg) was suspended in 1% Tween 80 in saline solution and was administered intraperitoneally (i.p.) 60 min before the test. Diazepam (DZ, Relanium, Polfa, Poland) at a dose of 1 mg/kg was diluted in 0.9% saline containing 1% Tween 80 and was administered subcutaneously (s.c.), 60 min before the test. Imipramine hydrochloride (30 mg/kg, Sigma-Aldrich was administered intraperitoneally (i.p.) 60 min before the test. D-amphetamine sulfate (3 mg/kg; Sigma-Aldrich, USA) was given subcutaneously (s.c.). Prior to administration, the agent was dissolved in saline and injected 30 min before the test. Control animals received an (i.p.) or (s.c.) injection of a respective vehicle. All compounds were injected in a manner generally accepted in experimental pharmacology, in an amount of 10 mL/kg body weight.
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10

Intraperitoneal Drug Administration Protocol

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The drugs used in this study included: ACTH-(1–24) (AnaSpec, San Jose, CA, USA), 100 μg/day dissolved in distilled water; imipramine hydrochloride 10 mg/kg (Sigma-Aldrich, St. Louis, MO, USA); lithium chloride 100 mg/kg (Sigma-Aldrich); control vehicle 0.9% saline (Fisher Healthcare, Hanover Park, IL, USA); and FatalPlus® (Vortech Pharmaceuticals, Dearborn, MI, USA), (constituents: pentobarbital sodium 390 mg/mL; propylene glycol 0.01 mg/mL; ethyl alcohol 0.29 mg/mL; benzyl alcohol (preservative) 0.20 mg/mL) 0.70 cc. Drugs were all delivered via intraperitoneal (i.p.) injection.
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