Citalopram hydrobromide

Manufactured by Merck Group

Sourced in United States

Citalopram hydrobromide is a laboratory chemical compound used in research and development applications. It is the hydrobromic acid salt form of the selective serotonin reuptake inhibitor (SSRI) drug, citalopram. Citalopram hydrobromide is commonly used as a reference standard in analytical and pharmacological studies.

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Citalopram (29 citations) Racemic citalopram hydrobromide (2 citations)

17 protocols using citalopram hydrobromide

Chronic Stress Effects on Mice

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To model physiological effects of chronic stress, we divided mice into four separate treatment groups. Mice in the untreated group received either standard mouse drinking water or subcutaneous saline injections during water restriction. Mice in the cortisol group received 40 μg/ml cortisol in the form of water-soluble hydrocortisone (Sigma-Aldrich, St. Louis, MO, United States) during ad lib water consumption (weeks 2–5 and 10) and 10 mg/kg cortisol subcutaneously during water restriction (weeks 5–9). To evaluate effects of a selective serotonin reuptake inhibitor, a separate group of cortisol-treated mice were also orally gavaged daily with 10 mg/kg citalopram hydrobromide (Sigma-Aldrich, St. Louis, MO, United States) during ad lib water consumption and injected subcutaneously with 10 mg/kg citalopram hydrobromide during water restriction. Finally, a fourth group of mice only received 10 mg/kg citalopram hydrobromide.

Indersmitten T., Schachter M.J., Young S., Welty N., Otte S., Nassi J.J., Lovenberg T., Bonaventure P, & Wyatt R.M. (2019). In vivo Calcium Imaging Reveals That Cortisol Treatment Reduces the Number of Place Cells in Thy1-GCaMP6f Transgenic Mice. Frontiers in Neuroscience, 13, 176.

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Intra-BNST and Systemic Pharmacological Interventions for Fear Conditioning

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Experiment 1: 15 min prior to fear conditioning training, animals received bilateral intra-BNST infusions of vehicle (0.5 µL/side; 0.9% sterile saline) or muscimol (4.4 nmol in 0.5 µL/side). This dose has been used previously to temporarily inactivate the BNST (Fendt et al., 2003 (link)). Experiment 2: 1 hour prior to fear conditioning training, animals received systemic injections of either 0.9% saline vehicle or citalopram hydrobromide (Sigma Aldrich) dissolved in vehicle (10mg/kg; i.p). Experiment 3: 1 hour prior to fear conditioning training, animals received systemic injections of either 0.9% saline vehicle or citalopram hydrobromide (Sigma Aldrich) dissolved in vehicle (10mg/kg; i.p). 15 minutes prior to fear conditioning training, animals received bilateral intra-BNST infusions of vehicle (40% DMSO and 60% saline solution, 0.25µL), or the 5-HT2C antagonist, RS-102221, 0.5µg per side in 0.25µl of a 40% DMSO and 60% saline solution. Solutions were infused at a rate of 0.1 µL/min through infusion cannula extending 1mm from the tip of the guide cannula that were attached to 1 µL Hamilton syringes with polyethylene tubing. The cannulae were left in place for 2 min after infusion to ensure the entire drug dose was delivered.

Pelrine E., Diana Pasik S., Bayat L., Goldschmiedt D, & Bauer E.P. (2016). 5-HT2C receptors in the BNST are necessary for the enhancement of fear learning by selective serotonin reuptake inhibitors. Neurobiology of learning and memory, 136, 189-195.

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Chronic SSRI and Hippocampal Muscimol Infusion

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Fluoxetine hydrochloride and Citalopram hydrobromide (Sigma-Aldrich) were dissolved in 0.9% sterile saline. Both drugs were administered in a dose of 10 mg/kg/ml based on previous studies^{14 (link),30 (link),31 (link)} and injected i.p. Chronic treatment consisted of daily administration during 21 days after fear conditioning or extinction protocols depending on the experiment performed.
Muscimol (1 µg/µl; Sigma Aldrich) was dissolved in phosphate-buffered saline (PBS) and bilaterally infused (0.5 µl/side) into dorsal hippocampus 15 min before memory retrieval.

Pedraza L.K., Sierra R.O., Giachero M., Nunes-Souza W., Lotz F.N, & de Oliveira Alvares L. (2019). Chronic fluoxetine prevents fear memory generalization and enhances subsequent extinction by remodeling hippocampal dendritic spines and slowing down systems consolidation. Translational Psychiatry, 9, 53.

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Punica granatum aqueous extract bioactivity

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In this study we used a whole fruit aqueous extract of Punica granatum (AE-PG) which was kindly provided by Nutracitrus S.L. (Elche, Alicante, Spain). The AE-PG was dissolved in saline solution 0.9% and administered orally (0.1, 1, 10, and 100 mg/kg doses); 17-β estradiol or E2 (Sigma-Aldrich, Toluca, Mexico) was dissolved in corn oil and injected subcutaneously (1.25, 2.5, 5, and 10 μg/rat). The citalopram hydrobromide (Sigma-Aldrich, Toluca, Mexico) was dissolved in saline solution 0.9% and injected intraperitoneally (2.5, 5, 10, and 20 mg/kg), and tamoxifen citrate (Sigma-Aldrich, Toluca, Mexico) was dissolved in corn oil and injected subcutaneously (15 mg/kg dose). The anesthetic 2,2,2-Tribrom-ethanol 2% (Sigma-Aldrich, Toluca, Mexico) was freshly prepared (for 25 mL, 0.5 g of tribrom-ethanol were dissolved in 2 mL of ethanol; thereafter, 23 mL of saline solution was slowly added while stirring) and administered intraperitoneally (10 mL/kg).

Valdés-Sustaita B., López-Rubalcava C., González-Trujano M.E., García-Viguera C, & Estrada-Camarena E. (2017). Aqueous Extract of Pomegranate Alone or in Combination with Citalopram Produces Antidepressant-Like Effects in an Animal Model of Menopause: Participation of Estrogen Receptors. International Journal of Molecular Sciences, 18(12), 2643.

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Quantitative Analysis of Antidepressants

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Methanol solutions of citalopram hydrobromide (1 mg/mL) and desmethylcitalopram hydrobromide (1 mg/mL) were purchased from Sigma-Aldrich (St. Louis, USA). Venlafaxine hydrochloride (VEN), an Internal Standard (IS) was supplied as courtesy of Moehs Iberica SL (Barcelona, Spain). Acetonitrile, methanol and formic acid were obtained from POCh (Gliwice, Poland). All chemicals and reagents were of UHPLC grade. Water was purified by double distillation in a Destamat^® Bi-18 system (Heraeus Quarzglas, Hanau, Germany).
A solid-phase equipment consisted of Chromabond 73015 (Macherey-Nagel, Duren, Germany) with vacuum pump NOZZ AT.18 (KNF Neuberger Inc, Trenton, USA). SPE columns Discovery C 18 (Supelco, Bellefonte, USA) were used for solid-phase extraction. High speed centrifuges, models EBA 20S (Hettich Lab Technology, Germany) and MPW-320 (MPW, Poland), a laboratory shaker 358 S (Elpin, Poland), and water bath LW-12 (Cabrolab Elektronik, Poland) were used for both SPE and LLE.

Dziurkowska E, & Wesolowski M. (2018). Simultaneous Quantification of Citalopram and its Main Metabolite,  Desmethylcitalopram, in Human Saliva by UHPLC. Current Analytical Chemistry, 14(6), 554-561.

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Toxicity and Growth Effects of Citalopram

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A toxicity curve was performed on the cells to determine the optimum concentration of citalopram hydrobromide (Sigma-Aldrich, MO, USA) that can be tolerated by the cells without changing their growth dynamics. Cells were cultured in growth media containing different concentrations of citalopram hydrobromide (10 μM, 50 μM, 90 μM, 120 μM, 160 μM, and 200 μM) for 48 hours. No effect was observed on cell growth kinetics or morphology below 120 μM, but at concentrations above 160 μM, an apoptotic-like cytotoxic effect was noted (Supplement 1). A 50 μM solution of citalopram hydrobromide was determined to be the maximum concentration that could be safely used without any possibility of inducing any change in growth kinetics. HEK-293 cells in the treatment group (in triplicates) were cultured with 50 μM citalopram hydrobromide for thirty days along with nontreated controls. All flasks were passaged and maintained under similar conditions as mentioned above for a period of thirty days.

Kanherkar R.R., Getachew B., Ben-Sheetrit J., Varma S., Heinbockel T., Tizabi Y, & Csoka A.B. (2018). The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells. International Journal of Genomics, 2018, 8929057.

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Radioligand Binding Assay Protocol

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[³H]5-hydroxytryptamine ([³H]5-HT), 80 Ci mmol⁻¹ and [³H]dihydroalprenolol, levo-[propyl-1,2,3–3H] hydrochloride, 80 Ci mmol⁻¹ were purchased from American Radiolabeled Chemicals, Inc. Unlabeled serotonin hydrochloride, L-tryptophan, paroxetine hydrochloride, citalopram hydrobromide, venlafaxine hydrochloride, cimetidine hydrochloride, reserpine, corticosterone, cortisol and phenelzine were purchased from Sigma-Aldrich. All other chemicals were of analytical grade. Bicinchoninic acid assay (BCA assay) reagents were purchased from Thermo Fisher Scientific. Tri Reagent solution was obtained from the Molecular Research Centre.

Karahoda R., Horackova H., Kastner P., Matthios A., Cerveny L., Kucera R., Kacerovsky M., Tebbens J.D., Bonnin A., Abad C, & Staud F. (2020). Serotonin homeostasis in the materno-foetal interface at term: Role of transporters (SERT/SLC6A4 and OCT3/SLC22A3) and monoamine oxidase A (MAO-A) in uptake and degradation of serotonin by human and rat term placenta. Acta physiologica (Oxford, England), 229(4), e13478.

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Radioactive Serotonin Binding Assay

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Tritium-labeled Serotonin creatinine sulfate (³H-serotonin; 28.3 Ci mmol⁻¹ and 41.3 Ci mmol⁻¹) and radiocarbon-labeled serotonin binoxalate (¹⁴C-serotonin; 54.0 mCi mmol⁻¹) were obtained from Perkin Elmer (Waltham, MA, USA). Serotonin creatinine sulfate, imipramine hydrochloride, citalopram hydrobromide, 3,4-methylenedioxymethamphetamine hydrochloride (MDMA, “Ecstasy”), L-ascorbic acid, and Hanks’ Balanced Salts Solution (HBSS) were obtained from Sigma-Aldrich (St. Louis, MO, USA). Pargyline hydrochloride was from Cayman Chemical (Ann Arbor, MI, USA). Other drugs were generous gifts from manufacturers.

Baković P., Kesić M., Perić M., Bečeheli I., Horvatiček M., George M., Čičin-Šain L., Desoye G., Wadsack C., Panzenboeck U, & Štefulj J. (2021). Differential Serotonin Uptake Mechanisms at the Human Maternal–Fetal Interface. International Journal of Molecular Sciences, 22(15), 7807.

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Neurotransmitter Binding Assay

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³H-serotonin (80 Ci/mmol), ³H-norepinephrine (20 Ci/mmol), and ³H-dopamine (60 Ci/mmol) were purchased from M.G.P. (Zlín, Czech Republic). Forskolin was obtained from Scintila, s.r.o. (Jihlava, CZ). Paroxetine hydrochloride, citalopram hydrobromide, sertraline hydrochloride, fluoxetine hydrochloride, fluvoxamine maleate, venlafaxine hydrochloride, phenelzine sulfate salt, entacapone, GBR 12935 dihydrochloride, nisoxetine hydrochloride, hydrocortisone, and decynium-22 were purchased from Sigma-Aldrich (St. Louis, USA). Pierce™ BCA Protein Assay Kit was purchased from Thermo Fisher Scientific (Waltham, United States). All other chemicals were of analytical grade.

Vachalova V., Karahoda R., Ottaviani M., Anandam K.Y., Abad C., Albrecht C, & Staud F. (2022). Functional reorganization of monoamine transport systems during villous trophoblast differentiation: evidence of distinct differences between primary human trophoblasts and BeWo cells. Reproductive Biology and Endocrinology : RB&E, 20, 112.

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Citalopram Effects on Stress-Induced Behavior

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Citalopram hydrobromide (Sigma-Aldrich) was stored in dimethyl sulfoxide (DMSO) stock solution and diluted in HEPES buffered saline (10 mg/kg, final DMSO concentration 0.05%). Vehicle injections were matched for DMSO concentration. To ensure that all behaviour and imaging findings were dissociated from the acute effects of the treatment, behaviour and imaging occurred 5 days following the completion of the stress protocol.

McGirr A., LeDue J., Chan A.W., Boyd J.D., Metzak P.D, & Murphy T.H. (2020). Stress impacts sensory variability through cortical sensory activity motifs. Translational Psychiatry, 10, 20.

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