Citalopram Research Articles

ChemInform Abstract: Copper‐Catalyzed Cyanoalkylative Cycloetherification of Alkenes to 1,3‐Dihydroisobenzofurans: Development and Application to the Synthesis of Citalopram.

AbstractA series of 1,3‐dihydroisobenzofurans (III) is readily prepared by copper‐catalyzed reaction of (2‐vinylaryl)methanols (I) with acetonitrile.

Multi-biomarker investigation to assess toxicity induced by two antidepressants on Dreissena polymorpha

Antidepressants are one of the main pharmaceutical classes detected in the aquatic environment. Nevertheless, there is a dearth of information regarding their potential adverse effects on non-target organisms. Thus, the aim of this study was the evaluation of sub-lethal effects on the freshwater mussel Dreissena polymorpha of two antidepressants commonly found in the aquatic environment, namely Fluoxetine (FLX) and Citalopram (CT). D. polymorpha specimens were exposed to FLX and CT alone and to their mixture (MIX) at the environmental concentration of 500ng/L for 14days. We evaluated the sub-lethal effects in the mussel soft tissues by means of a biomarker suite: the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the activity of the phase II detoxifying enzyme glutathione-S-transferase (GST). The oxidative damage was evaluated by lipid peroxidation (LPO) and protein carbonylation (PCC), while genetic damage was tested on D. polymorpha hemocytes by Single Cell Gel Electrophoresis (SCGE) assay, DNA diffusion assay and micronucleus test (MN test). Finally, the functionality of the ABC transporter P-glycoprotein (P-gp) was measured in D. polymorpha gills. Our results highlight that CT, MIX and to a lesser extent FLX, caused a significant alteration of the oxidative status of bivalves, accompanied by a significant reduction of P-gp efflux activity. However, only FLX induced a slight, but significant, increase in apoptotic and necrotic cell frequencies. Considering the variability in biomarker response and to perform a toxicity comparison of tested molecules, we integrated each endpoint into the Biomarker Response Index (BRI). The data integration showed that 500ng/L of FLX, CT and their MIX have the same toxicity on bivalves.

Solid-state characterization and pharmaceutical compatibility between citalopram and excipients using thermal and non-thermal techniques

Differential scanning calorimetry (DSC) has been used in combination with powder X-ray diffraction (PXRD) and solid-state nuclear magnetic resonance (SSNMR) for evaluation of drug–excipient interaction. This study aimed to evaluate the antidepressive citalopram hydrobromide and the most usual excipient commonly used for the evaluation of their compatibility in binary mixtures. The TG/DTG curves reveal that citalopram is thermally stable up to 230 °C, presenting a sharp endothermic peak at 183 °C (Tonset = 185 °C) that corresponds to its melting point. Only for citalopram–lactose binary mixture was observed dislocation of the melting event in the DSC curves; however, this change has not indicated to be an interaction between the components in this case, but an overlap of events of lactose and citalopram. PXRD pattern suggests that no interaction is present between individual components that still showing the same crystalline structure for citalopram. The SSNMR spectrum assignment was done based on computational prediction of chemical shifts comparing it with its original spectrum. The chemical shifts confirmed the expected structure. Therefore, since changes in chemical shift are smaller than 1 ppm, no evidence of chemical interaction between the components of each binary mixture was confirmed.

Electrochemical determination of citalopram on new Schiff base functionalized magnetic Fe3O4 nanoparticle/MWCNTs modified glassy carbon electrode

In this study, a new glassy carbon electrode chemically modified with multi-walled carbon nanotubes (MWCNTs) and core-shell structured Fe3O4@[(EtO)3Si–L] was constructed and used for the sensitive and selective electrochemical determination of trace amounts of citalopram (CT). New Schiff base functionalized magnetic Fe3O4 nanoparticle was prepared to use as an effective ionophore in electrochemical responses of the potentiometric sensor for the determination of CT in aqueous solutions. The influences of the effective parameters such as working solution pH and scan rate on the electrochemical behavior of modified electrode were investigated. This electrochemical sensor responds to CT in the wide linear range of 3.00×10−7 to 1.00×10−1molL−1. The detection limit of 5.32×10−8molL−1 was obtained at pH range 3–11. The proposed sensor has a fast response time and can be applied for at least 4months without any significant divergences in the currents. It shows simple preparation, good reproducibility (RSD=0.73%), long-term stability (RSD=1.31%), accuracy in analysis and stable electrochemical sensing of CT in the presence of a large number of vitamins, carboxylic acids, ions and drugs.

Switched drugs similarly cost effective after citalopram failure

Switched drugs similarly cost effective after citalopram failure

Identification of biotransformation products of citalopram formed in activated sludge

Citalopram (CTR) is a worldwide highly consumed antidepressant which has demonstrated incomplete removal by conventional wastewater treatment. Despite its global ubiquitous presence in different environmental compartments, little is known about its behaviour and transformation processes during wastewater treatment. The present study aims to expand the knowledge on fate and transformation of CTR during the biological treatment process. For this purpose, batch reactors were set up to assess biotic, abiotic and sorption losses of this compound. One of the main objectives of the study was the identification of the formed transformation products (TPs) by applying suspect and non-target strategies based on liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). The complementary use of reversed phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) for the identification of polar TPs, and the application of in-house developed quantitative structure-retention relationship (QSRR) prediction models, in addition to the comprehensive evaluation of the obtained MS/MS spectra, provided valuable information to support identification. In total, fourteen TPs were detected and thirteen of them were tentatively identified. Four compounds were confirmed (N-desmethylCTR, CTR amide, CTR carboxylic acid and 3-oxo-CTR) through the purchase of the corresponding reference standard. Probable structures based on diagnostic evidence were proposed for the additional nine TPs. Eleven TPs are reported for the first time. A transformation pathway for the biotransformation of CTR was proposed. The presence of the identified TPs was assessed in real wastewater samples through retrospective analysis, resulting in the detection of five compounds. Finally, the potential ecotoxicological risk posed by CTR and its TPs to different trophic levels of aquatic organisms was evaluated by means of risk quotients.

Fabrication a new modified electrochemical sensor based on Au–Pd bimetallic nanoparticle decorated graphene for citalopram determination

This paper proposes a simple approach for sensing of citalopram (CTL) using gold–palladium bimetallic nanoparticles (Au–PdNPs) decorated graphene modified gold electrode. Au–PdNPs were deposited at the surface of a graphene modified gold electrode with simple electrodeposition method. The morphology and the electrochemical properties of the modified electrode were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), energy dispersion spectroscopy (EDS), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square wave voltammetry (SWV). The novel sensor exhibited an excellent catalytic activity towards the oxidation of CTL. The oxidation peak current of CTL, was linear in the range of 0.5–50μM with a detection limit 0.049μM with respect to concentration of citalopram. The proposed sensor was successfully applied for determination of CTL tablet and human plasma samples with satisfactory results.

Simultaneous determination of ambroxol and salbutamol in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry assay method was developed for simultaneous determination of ambroxol and salbutamol in human plasma using citalopram hydrobromide as internal standard (IS). The sample was alkalinized with ammonia water (33:67, v/v) and extracted by single liquid-liquid extraction with ethyl acetate. Separation was achieved on Waters Acquity UPLC BEH C18 column using a gradient program at a flow rate of 0.2 mL/min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the ion transitions m/z 378.9 → 263.6 (ambroxol), m/z 240.2 → 147.7 (salbutamol) and m/z 325.0 → 261.7 (IS). The total analytical run time was relatively short (3 min). Calibration curves were linear in the concentration range of 0.5-100.0 ng/mL for ambroxol and 0.2-20.0 ng/mL for salbutamol, with intra- and inter-run precision (relative standard deviation) <15% and accuracy (relative error) ranging from 97.7 to 112.1% for ambroxol and from 94.5 to 104.1% for salbutamol. The method was successfully applied in a clinical pharmacokinetic study of the compound ambroxol and salbutamol tablets.

Effects of antidepressant therapy on serotonin and tryptophan hydroxylase 2 in ovariectomized rats with depressive disorder

Obiective To investigate the effects of antidepressant therapy on whole regulating function of serotonin and tryptophan hydroxylase 2 system in ovariectomized(OVX) rats with depressive disorder. Methods seventy-two female Sprague-Dawley rats were used as subjects.The rats were randomly divided into 8 groups as following: Sham operation group (Sn), depression group(Dn), the OVX group(On), OVX with depression group(ODn), OVX with depression+ sertraline group(ODs), OVX with depression+ citalopram group(ODx), OVX with depression+ venlafaxine group(ODw) , OVX with depression+ reboxetine group(ODr). Rats in group OVX and group OVX with depression were ovariectomized.Rats in group with depression were exposed to the chronic unpredictable mild stress (CUMS). Open-field test and sugar consumption experiment were tested on all rats before the experiment and the 28th day of experiment.The expression of TPH2 mRNA was measured with RT-PCR, and the expression of TPH2 protein was detected by Western blot.The concentration of 5-HT was detected by ELISA. Results (1) After exposure of CUMS, the scores of motion and percentage of sugar consumption experiment in Dn group were decreased contrast to the Sn group(P<0.05) , and the scores in ODn group were decreased compared with the on group(P<0.05). (2)The protein and gene expression of THP2 in On and Dn group were decreased contrast to the Sn group (P<0.05). The protein and gene expression of THP2 in ODn were decreased compared with the on group (P<0.05). The protein and gene expression of THP2 in ODs(protein (0.68±0.07); gene (0.87±0.09)), ODx(protein (0.71±0.05); gene (0.84±0.17)), ODw(protein (0.69±0.04); gene (0.88±0.16)) and ODr(protein (0.53±0.07); gene (0.70±0.15)) were increased compared with the ODn(protein (0.31±0.09); gene (0.56±0.16)) group(P<0.05). (3)The concentration of 5-HT of hippocampus and serum in Dn and On group were decreased contrast to the Sn group (P<0.05). The concentration of 5-HT of hippocampus and serum in ODs, ODx, ODw and ODr group was increased compared with the ODn group (P<0.05). Conclusion The antidepressants can up-regulate the expression of THP2 and the concentration of 5-HT in the OVX rats with depressive disorder.Sertralin is stronger however Reboxetine Mesylate is the poorest. Key words: Antidepressant; Depressive disorder rats model; Ovariectomized rats model; Tryptophan hydroxylase 2; 5-hydroxytryptamine

Citalopram Guidance in the VA: Unintended Consequences

Guidance to help clinicians “choose wisely” by comparing benefits and harms of treatments can have mixed results at times. In 2011, the FDA and

Synthesis of Citalopram

Synthesis of Citalopram

The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats.

The use of a combined therapy with low doses of estrogens plus antidepressants to treat depression associated to perimenopause could be advantageous. However the use of these combinations is controversial due to several factors, including the time of intervention in relation to menopause onset. This paper analyzes whether time post-OVX influences the antidepressant-like action of a combination of ethynyl-estradiol (EE2) and citalopram (CIT) in the forced swim test (FST). Middle-aged (15 months old) female Wistar rats were ovariectomized and after one or three weeks treated with EE2 (1.25, 2.5 or 5.0 µg/rat, s.c.; −48 h) or CIT (1.25, 2.5, 5.0 or 10 mg/kg, i.p./3 injections in 24 h) and tested in the FST. In a second experiment, after one or three weeks of OVX, rats received a combination of an ineffective dose of EE2 (1.25 µg/rat, s.c., −48 h) plus CIT (2.5 mg/kg, i.p./3 injections in 24 h) and subjected to the FST. Finally, the uteri were removed and weighted to obtain an index of the peripheral effects of EE2 administration. EE2 (2.5 or 5.0 µg/rat) reduced immobility after one but not three weeks of OVX. In contrast, no CIT dose reduced immobility at one or three weeks after OVX. When EE2 (1.25 µg/rat) was combined with CIT (2.5 mg/kg) an antidepressant-like effect was observed at one but not three weeks post-OVX. The weight of the uteri augmented when EE2 was administrated three weeks after OVX. The data suggest that the time post-OVX is a crucial factor that contributes to observe the antidepressant-like effect of EE2 alone or in combination with CIT.

Crystal structure of citalopram hydrobromide, C20H22FN2OBr

The crystal structure of citalopram hydrobromide has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional theory techniques. Citalopram hydrobromide crystallizes in space groupP21/c(#14) witha= 10.766 45(6),b= 33.070 86(16),c= 10.892 85(5) Å,β= 90.8518(3)°,V= 3878.03(4) Å3, andZ= 8. N–H⋯Br hydrogen bonds are important to the structure, but the crystal energy is dominated by van der Waals attraction. The powder pattern was submitted to International Centre for Diffraction Data for inclusion in the Powder Diffraction File™.

Antidepressant Use and Risk for Adverse Cardiovascular Outcomes

Observational studies have suggested a link between selective serotonin reuptake inhibitors (SSRIs) and excess risk for adverse cardiovascular (CV) events in older adults (age, ≥65); whether this is true in younger adults is unclear. Furthermore, the FDA has warned against prescribing the SSRI citalopram at doses >40 mg daily because of risk for QT-interval prolongation. U.K. researchers …

Effects of antidepressants on osteoporosis related protein OPG, RANKL and RANK in ovariectomized rat model with depressive disorder

Objective To investigate the effects of antidepressant therapy on whole regulating function of OPG/RANKL/RANK system in ovariectomized(OVX) rat model with depressive disorder. Methods Forty sexually mature female SD rats were used as subjects. The rats were randomly divided into 8 groups as following: sham group(Sn), depression group(Dn), the OVX group(On), the OVX with depression group(ODn), OVX with depression + sertraline group (ODs), and OVX with depression + citalopram (ODx), OVX with depression + reboxetine group(ODr), OVX with depression + venlafaxine group(ODw). Bilateral oophorectomy was applied to establish the ovariectomized rats model.Chronic unpredictable mild stress(CUMS) was used to estalish depression model. Open-field test and sugar consumption experiment were applied before the experiment and the 28th day of the experiment. Immunohistochemistry and Quantitative Real-time PCR were used to observe the expression of OPG, RANKL and RANK. Results After chronic unpredictable mild stress the scores of horizontal motion, vertical motion and percentage of sugar consumption experiment in Dn group were decreased contrast to the in control Sn group (P<0.05)and the scores in ODn group were decreased in contrast to the On group (P<0.05). The protein and gene expression of RANK in Dn group and On group were increased in contrast to the Sn group (P<0.05). The protein and gene expression of RANKL in Dn group and On group were increased in contrast to the Sn group (P<0.05). The gene expression of OPG in ODs group(5.94±0.79), ODw group(5.99±1.08) and ODr group(6.59±0.69)was decreased in contrast to the ODn group(4.96±0.51)(P<0.05). The gene expression of RANK in ODs group(2.82±0.23), ODx group(3.03±0.04)was increased in contrast to the ODn group(3.44±0.18)(P<0.05). The gene expression of RANKL in ODs group(4.82±0.94), ODx group(5.00±0.82) and ODw group(5.23±0.88)was decreased in contrast to the ODn group(3.69±0.69)(P<0.05). Conclusion The expression of RANK and RANKL in femoral neck is increased both in depressive disorder model rats and ovariectomized model rats.The antidepressant can up-regulate the expression of RANK, and down-regulate the expression of OPG and RANKL in the OVX with depression group. Of the effect, sertraline is the strongest, however reboxetine mesylate is the poorest. Key words: Antidepressant; Depressive disorder rats model; Ovariectomized rats model; Osteoprotegerin; Receptor activator of NF-κB

Optimization of ultrasound-assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplets by experimental design methodologies for determination of three anti-anxiety drugs in human serum and urine samples by high performance liquid chromatography

A novel coupling of ultrasound-assisted dispersive liquid–liquid microextraction based on solidification of floating organic droplets (UA-DLLME-SFODs) with high performance liquid chromatography (HPLC) was developed for the simultaneous preconcentration and determination of citalopram (CIT), diazepam (DIZ), and sertraline (SER) in their tablets and in the human serum and urine samples. In this proposed procedure, 1-undecanol and ethanol were used as the extraction and disperser solvents, respectively. Several parameters affecting the extraction efficiency were investigated using the Plackett–Burman (PB) factorial design as a screening design. The variables showing significant effects on the analytical response were the pH value for the sample solution and the volume of the extraction solvent; they were optimized using the central composite face-centered design (CCFD). For validation of the technique, its accuracy, precision, limit of detection (LOD), linearity, and sensitivity were evaluated. Also the limits of quantification (LOQs) were 1.3, 2.7, and 1.2ngmL−1 for CIT, DIZ, and SER, respectively. The extraction recovery percentages for all the examined drugs were above 92.9 with acceptable relative standard deviations (RSDs). The proposed methodology was successfully applied to the determination of these drugs in their tablets and in the human serum and urine samples.

Colorimetric chiral discrimination and determination of S-citalopram based on induced aggregation of gold nanoparticles

A simple and reliable colorimetric method for the quantitative determination of citalopram (CIT) enantiomers in aqueous solution using gold nanoparticles as a colorimetric probe was presented. S-citalopram induced aggregation of citrate capped AuNPs resulted in a decrease in the plasmon absorption at 520nm and the formation of a broadened surface plasmon band around 600–700nm. The results show that the colorimetric system possesses a very well selectivity toward S-citalopram compare to the R-citalopram as evidenced by the fact that there is the same color change from S-citalopram and (RS)-citalopram, and significant UV–vis spectral shift. The experimental conditions were optimized and the results show that S-citalopram can be determined in a linear range 2.5×10−6–6.0×10−4M with correlation coefficients of 0.9963 and limit of detection 2.1×10−6M.

Citalopram attenuates tau hyperphosphorylation of cortex and memory deficits in social isolation-reared rats

Objective To explore the effect of citalopram on tau phosphorylation and memory deficits induced by social isolation (SI) in adult rats. Methods Sixty Sprague-Dawley adult rats (8 months) were grouped or isolation reared for six-weeks. Following the initial two-week period of rearing, citalopram (10 mg/kg, i.p.) was administered for 4 weeks. Novel object recognition test, Western blot and ELISA were used to detect recognitive function, the levels of tau and GSK-3β protein, and melatonin level respectively. Results In the novel object recognition test, compared with the citalopram group(0.71±0.05) and housed group(0.73±0.13), discrimination ratio(0.48±0.15) in SI group was significant decreased (P<0.05). Tau hyperphosphorylation at Tau-1 ((0.88±0.11)), Ser396 (3.94±0.74) episodes were found and almost reversed by citalopram at Tau-1 (1.56±0.17), Ser396 (2.31±0.24) episodes in SI group. Compared with GH group, the total level of GSK-3β(1.12±0.09) was significantly increased, while the level of Ser9-phosphorylated GSK-3β (inactive form) (0.47±0.11) was significantly decreased in the SI group, both of which were reversed by citalopram (GSK-3β (0.87±0.08) and Ser9-phosphorylated GSK-3β (0.80±0.07)). The melatonin level was decreased in SI group ((359.54±18.80)pg/ml), and citalopram could partly restore the level of melatonin (418.15±18.72)pg/ml, P<0.05). Conclusion The results demonstrate that citalopram increases the level of melatonin which negatively regulates GSK-3β and attenuates tau hyperphosphorylation and memory deficits induced by SI in adult rats. Key words: Social isolation; tau protein; Citalopram; Alzheimer's disease; Melatonin

Maternal Pharmacokinetics and Fetal Disposition of (±)-Citalopram during Mouse Pregnancy.

While selective-serotonin reuptake inhibitor (SSRI) antidepressants are commonly prescribed in the treatment of depression, their use during pregnancy leads to fetal drug exposures. According to recent reports, such exposures could affect fetal development and long-term offspring health. A central question is how pregnancy-induced physical and physiological changes in mothers, fetuses, and the placenta influence fetal SSRI exposures during gestation. In this study, we examined the effects of gestational stage on the maternal pharmacokinetics and fetal disposition of the SSRI (±)-citalopram (CIT) in a mouse model. We determined the maternal and fetal CIT serum concentration–time profiles following acute maternal administration on gestational days (GD)14 and GD18, as well as the fetal brain drug disposition. The results show that pregnancy affects the pharmacokinetics of CIT and that maternal drug clearance increases as gestation progresses. The data further show that CIT and its primary metabolite desmethylcitalopram (DCIT) readily cross the placenta into the fetal compartment, and fetal exposure to CIT exceeds that of the mother during gestation 2 h after maternal administration. Enzymatic activity assays revealed that fetal drug metabolic capacity develops in late gestation, resulting in elevated circulating and brain concentrations of DCIT at embryonic day (E)18. Fetal exposure to the SSRI CIT in murine pregnancy is therefore influenced by both maternal gestational stage and embryonic development, suggesting potential time-dependent effects on fetal brain development.

A novel voltammetric sensor for citalopram based on multiwall carbon nanotube/(poly(p-aminobenzene sulfonic acid)/β-cyclodextrin)

Multi-walled carbon nanotube (MWCNTS) coated with poly p-aminobenzene sulfonic acid/β-cyclodextrin (p-ABSA/β-CD) film was used as an effective strategy for modification of the surface of glassy carbon electrode (GCE). Electrochemical study and determination of citalopram (CT) were investigated at the p (p-ABSA)/β-CD/MWCNT/GC using cyclic and differential pulse anodic stripping voltammetric techniques. The results indicate that the p (p-ABSA)/β-CD/MWCNT/GC significantly enhanced the oxidation peak current of CT. The modified electrode was characterized by electrochemical impedance spectroscopy (EIS), scanning electron microscopy(SEM) and cyclic voltammetry (CV).The fabricated electrochemical sensor exhibits a fast and reversible linear response toward CT within the concentration ranges of 90nM–1μM, 1–11μM and 11–100μM with correlation coefficients greater than 0.99 and detection limit of 44nM. The resulting functionalized polymer film features interesting electrochemical properties such good recovery, reproducibility and selectivity toward CT. The applicability of the proposed sensor was tested by determination of CT in pharmaceutical combinations and human body fluids.