Citalopram Research Articles

Elevated temperature increases the susceptibility of D. magna to environmental mixtures of carbamazepine, tramadol and citalopram

The joint risks assessment of thermal stress and rising loads of pharmaceuticals (PhACs) in surface waters is a relevant topic in aquatic ecotoxicology. This study investigated the relevance of increased water temperature to alter the acute toxicity of environmentally relevant carbamazepine (CBZ), citalopram (CIT) and tramadol (TRA) concentrations as mixtures (ECs) and delayed outcomes in Daphnia magna. Responses of detoxification and antioxidant pathways in premature daphnids post an acute 24 h (pulsed) exposure to the PhACs mixtures and delayed responses as the reproductive output over 14 days recovery were investigated under 21- and 26 °C incubation. Biphasic modulation in glutathione S-transferase (GST) activity and significant inhibition of superoxide dismutase (SOD) activity were observed in both thermal regimes with significant shift in effective thresholds from 10-fold ECs at 21 °C to ECs at 26 °C incubation. Significant induction in catalase (CAT) activity and oxidative stress development were recorded at elevated temperatures from the 10-fold ECs dose onward. Pulsed exposures at 26 °C also led to significant decrease in the reproduction of daphnids above the 10-fold ECs of PhACs. The Integrated Biomarker Response scoring (IBRv2) approach outlined a 1.8-fold increase in alterations of daphnids exposed to 100-fold ECs of PhACs at 26 °C.

Assessing the Neurodevelopmental Impact of Fluoxetine, Citalopram, and Paroxetine on Neural Stem Cell-Derived Neurons

Background/Objectives: Many pregnant women globally suffer from depression and are routinely prescribed selective serotonin reuptake inhibitors (SSRIs). These drugs function by blocking the re-uptake of serotonin by the serotonin transporter (SERT) into neurons, resulting in its accumulation in the presynaptic cleft. Despite a large amount of research suggesting a potential link to neurodevelopmental disorders in children whose mothers took these drugs during pregnancy, their possible adverse effects are still debated, and results are contradictory. On the other hand, there is an immediate need for improved cell-based models for developmental neurotoxicity studies (DNT) to minimize the use of animals in research. Methods: In this study, we aimed to assess the effects of clinically relevant concentrations of paroxetine (PAR), fluoxetine (FLX), and citalopram (CIT)—on maturing neurons derived from human neural stem cells using multiple endpoints. Results: Although none of the tested concentrations of FLX, CIT, or PAR significantly affected cell viability, FLX (10 µM) exhibited the highest reduction in viability compared to the other drugs. Regarding neurite outgrowth, CIT did not have a significant effect. However, FLX (10 µM) significantly reduced both mean neurite outgrowth and mean processes, PAR significantly reduced mean processes, and showed a trend of dysregulation of multiple genes associated with neuronal development at therapeutic-relevant serum concentrations. Conclusions: Transcriptomic data and uptake experiments found no SERT activity in the system, suggesting that the adverse effects of FLX and PAR are independent of SERT.

A quality by design paradigm, novel, and fast LC-MS/MS method to quantify vortioxetine in rat brain homogenate and its assessment of greenness, whiteness, and blueness tools

Vortioxetine (VOR) is an antidepressant drug with multimodal mechanism of action. In this work a sensitive and simple bioanalytical LC-MS/MS method for analysis of VOR in spiked rat brain tissue was developed and validated. Chromatographic analyses were performed in isocratic mode, and Citalopram (CT) was found as a suitable internal standard. Supelco Ascentis® Express Phenyl-Hexyl column was used as stationary phase, and the mobile phase was 0.15 % formic acid in acetonitrile:water (55:45, v/v). A Box-Behnken Design − based method optimization was applied to explore the impact of analytical conditions on chromatographic separation of VOR and CT. Detection was realized via a triple quadrupole LC-MS/MS system; the mass transition ion-pair has been followed as m/z 299.05 → 149.90 for VOR, m/z 325.20 → 109.05 for CT. Analytical method validation was performed according to International Council for Harmonisation (ICH) guideline M10 on bioanalytical method validation. The calibration curve was within the range of 30 to 450 ng/mL. LOD and LLOQ were calculated at 10 and 30 ng/mL, respectively. Recovery was 90 % for the lower limit of quantification and between 98 % to 105 % for the other concentration levels. Total run time was 5 min, retention times of citalopram and vortioxetine were 2.4 and 3.1 min, respectively, and a good chromatographic separation was obtained under optimal conditions. The solvents used to make the method greener were evaluated with the Green Solvent Selection Tool and Green Index Spider chart. The AGREE score for the greenness of the developed method was calculated as 0.61 and was also evaluated with the ComplexGAPI pictogram. The BAGI score for blueness was calculated as 72.5, and the RGBfast score for whiteness was calculated as 50. The method was determined to be most green, white, and blue.

Drug-Drug Interactions of Selective Serotonin Reuptake Inhibitors: A Pharmacovigilance Study on Real-World Evidence from the EudraVigilance Database.

As the most common psychiatric symptom, depression represents a subject of high interest for the medical community. Background/Objectives: International guidelines consider selective serotonin reuptake inhibitors (SSRIs) the first-line treatment of depression. Although having better efficacy and tolerability in comparison to tricyclic antidepressants or monoamine oxidase inhibitors, the diversity and potential severity of adverse effects and interactions manifested by SSRIs, combined with the frequency of prescriptions, lead to the necessity of evaluating real-world data. The aim of this study was to identify and evaluate the drug interactions reported in EudraVigilance (EV) for the six SSRIs representatives that are authorized in Europe: fluoxetine (FXT), fluvoxamine (FVM), citalopram (CIT), escitalopram (ESC), paroxetine (PAR) and sertraline (SER). The entire class of SSRIs was examined as a comparator to identify whether one of the representatives was more prone to reporting. Methods: Descriptive analysis and disproportionality analysis were conducted on data extracted from the EV database. Results: A total of 326,450 adverse reactions (ADRs) were reported for the SSRIs group. Approximately a quarter of these (n = 83,201; 25.46%) were reported for SER and 22.37% (n = 73,131) for PAR. Of the total ADRs reported, 2.12% (n = 6925) represent preferred terms related to drug-drug interactions (DDIs): SER (n = 1474; 22.37%), CIT (n = 1272, 19.86), and FXT (n = 1309, 19.83%). Specific ADRs related to inhibitory activity represent 0.98%, and for potentiating activity, 1.89%. Conclusions: Although representing a small value of the total ADRs, DDIs may be related to severe outcomes. Awareness should be raised for this category of ADRs that can be reduced by the joined efforts of physicians and pharmacists.

Tailor-Made Doses of Pharmaceuticals by Tunable Modular Design: A Case Study on Tapering Antidepressant Medication.

An abrupt cessation of antidepressant medication can be challenging due to the appearance of withdrawal symptoms. A slow hyperbolic tapering of an antidepressant, such as citalopram hydrobromide (CHB), can mitigate the withdrawal syndrome. However, there are no viable dosage forms on the market to implement the tapering scheme. A solution using a tunable modular design (TMD) approach to produce flexible and accurate doses of CHB is proposed. This design consists of two parts: 1) a module with a fixed amount of preloaded CHB in a freeze-dried polymer matrix, and 2) fine-tuning the CHB dose by inkjet printing. A noncontact food-grade printer, used for the first time for printing pharmaceuticals, is modified to allow for accurate printing of the highly concentrated CHB ink on the porous CHB-free or CHB-preloaded modules. The produced modules with submilligram precision are bench-marked with commercially available CHB tablets that are manually divided. The TMD covers the entire range of doses needed for the tapering (0.5-23.8mg). The greatest variance is 13% and 88% when comparing the TMD and self-tapering, respectively. Self-tapering is proven inaccurate and showcases the need for the TMD to make available accurate and personalized doses to wean off treatment with CHB.

Antinociceptive Evaluation of Antidepressants (Cita- lopram, Duloxetine and Amitriptyline) in a Mouse Model of Acute Pain

Introduction: Acute pain is a pervasive and debilitating symptom affecting the general population as well as depressed patients who suffer even more from pain and fatigue. Aims and Objectives: To evaluate the antinociceptive effect induced by antidepressants (Citalopram, Duloxetine and Amitriptyline) in acute pain induced in mice. Place and Duration of study: Animal Research Laboratory of University of Lahore. Study Period: 2018- 2019 Material and Methods: An experimental animal study was carried out on 25 albino mice. The mice were divided into 5 groups; Group 1: Positive Control (PC), Group 2: Ibuprofen (IBO) (Standard) 80mg/kg, Group3: Citalopram (CTP)3mg/kg, Group 4: Duloxetine (DXT) 25mg/kg, Group 5: Amitriptyline (AMT) 15mg/kg. Groups 2-5 were administered drugs orally through a feeding tube as per group designation while Group 1: Control was given an equivalent amount of normal saline. One hour post treatment with test drugs, all Groups (1-5) were injected 10 ml/ kg of 2% acetic acid I/P and number of writhing movements consisting of contraction of abdominal muscles leading to extension of hind limb and periodic arching of body as well as paw licking behavior were counted for 20 minutes at 5- minute interval, using hand tally counter. Degree of analgesia was calculated by using formula of percentage effectiveness. Data was entered and analyzed utilizing SPSS version 21, p?0.05 was taken as significant. Results: Ibuprofen completely eliminated the nociceptive outcome of diluted acetic acid in writhing and licking of experimental animals. Citalopram, showed maximum decreasing effect (95%-96%) in writhing in 5-20 min. However, its effect in paw licking was low. Duloxetine showed 70% to 90% decrease in writhing at 5-20 min whereas 100 % inhibition of paw-licking was observed at 5 to 20 minutes. The writhing effect of amitriptyline was 77%-90% at 5-20 min and paw licking effect was 80-90 % at 5-20 min. Conclusion: Amitriptyline, duloxetine and citalopram have significant effect in reducing the acute nociceptive pain and may be utilized as analgesic in acute state of pain.

Dysregulation of adipogenesis and disrupted lipid metabolism by the antidepressants citalopram and sertraline

Selective Serotonin Reuptake Inhibitors (SSRIs) are widely used medications for the treatment of major depressive disorder. However, long-term SSRI use has been associated with weight gain and altered lipid profiles. These findings suggest that SSRIs may have negative effects on metabolism. Exposure to certain chemicals called ‘obesogens’ is known to promote lipid accumulation and obesity by modulating adipogenesis. Here, we investigated whether citalopram (CIT) and sertraline (SER) interfere with the process of adipogenesis, using human mesenchymal stem cells (MSCs) in a 2D and a 3D model. Assessment of intracellular lipid accumulation by fluorescence staining was used as a measure for enhanced adipogenesis. To explore possible mechanisms behind SSRIs' effects, receptor mediated activity was studied using responsive cell lines for various nuclear receptors. Furthermore, RNA sequencing was performed in the 3D model, followed by differential gene expression and pathway analysis. A dose dependent increase in lipid accumulation was observed in both models with CIT and SER. For the 3D model, the effect was seen in a range close to reported steady-state plasma concentrations (0.065–0.65 μM for SER and 0.12–0.92 μM for CIT). Pathway analysis revealed unexpected results of downregulation in adipogenesis-related pathways and upregulation in phospholipids and lysosomal pathways. This was confirmed by an observed increase in lysosomes in the 2D model. Our findings suggest lysosomal dysfunction and disrupted lipid metabolism in mature adipocytes, leading to excessive phospholipid synthesis. Moreover, important adipogenic processes are inhibited, potentially leading to dysfunctional adipocytes, which might have implications in the maintenance of a healthy metabolic balance.

DEVELOPMENT OF A FAST LIQUID CHROMATOGRAPHY METHOD WITH A CHEMOMETRIC APPROACH BASED ON BOX-BEHNKEN DESIGN FOR THE DETERMINATION OF ANTIDEPRESSANTS IN PHARMACEUTICAL FORMULATIONS

Objective: The objective of this work was to develop a liquid chromatographic method for the quantification of antidepressants, namely duloxetine (DXN), fluoxetine (FXN), citalopram (CIT), paroxetine (PXN), and sertraline (SRN), by a chemometric approach based on Box-Behnken design. Material and Method: After initial experiments to determine significant parameters, a Box-Behnken design consisting of 17 experiment sets was carried out. All separations were conducted using an Agilent Poroshell 120 EC-C18 analytical column (75 mm × 4.6 mm × 2.7 µm). Result and Discussion: The optimum levels of pH, acetonitrile ratio, and flow rate were determined with the desirability function as 2.7, 38%, and 1.1 ml/min, respectively. The differences (<8%) between predicted optimum responses and experimentally obtained results proved the model's suitability. Limits of detection and limits of quantification values were in the ranges of 0.17-0.29 µg/ml and 0.53-0.89 µg/ml, respectively. The feasibility of the technique was proven by analyzing PXN and DXN formulations.

Removal of selective serotonin reuptake inhibitor using magnetic graphene oxide derivatives: Adsorption study in low drug concentration using HPLC quantification, in vitro safety, and phytotoxicity

Citalopram (CIT) is a drug widely used around the world in the treatment of depression. Due to the high toxicity of CIT and the failure of the methods used in treatment plants to purify water, the removal of this pollutant from the environment is very necessary. In this study, the removal of CIT was performed using graphene oxide (GO) and magnetic graphene oxide (GO·Fe3O4 1:1, 1:5, and 1:10). Moreover, the adsorption of CIT was accomplished at low drug concentrations, and the safety of biological and phytological adsorbents was investigated. The characteristics of the adsorbents were analyzed through SEM and TEM images, XRD, EDS, XPS, FTIR, Raman, VSM and the analysis revealed the spectra and signal characteristics of GO and GO·Fe3O4. The GO·Fe3O4 1:1 showed the highest adsorption capacity of 97.92 mg g−1 and removal percentage (98%). The pH, initial concentration, and glucose natural organic matter did not significantly affect the adsorption. The ionic strength and high dosages of GO·Fe3O4 1:1 disfavors the adsorption. Pseudo-second-order (PSO) and Liu models suggest that adsorption occurs at heterogeneous surfaces. The thermodynamic study confirms that CIT adsorption onto GO·Fe3O4 was spontaneous and exothermic. The in vitro assays evidenced that the complex, after adsorption, decreases the genotoxicity and the oxidative stress caused by CIT. Finally, the complex after adsorption does not show phytotoxic for L. sativa seeds. These findings have significant relevance for the safe use of GO·Fe3O4 1:1, allowing the employ in water remediation processes and their biocompatibility for biological applications.

Establishment and Validation of a Transdermal Drug Delivery System for the Anti-Depressant Drug Citalopram Hydrobromide.

To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant.

Differences in the response of Chlorella pyrenoidosa to three antidepressants and their mixtures in different light-dark start cycles.

The use of antidepressants is increasing along with the continuing spike in the prevalence of depression worldwide. As a result, more and more antidepressants are entering the water and probably does harm to the aquatic organisms and even human health. Therefore, three antidepressants, including fluoxetine (FLU), citalopram (CIT), and aspirin (APC), were selected to investigate the toxic risks of antidepressants and their mixtures to a freshwater green alga Chlorella pyrenoidosa (C. pyrenoidosa). Due light is critical for the growth of green algae, six different light-dark cycle experiments were constructed to investigate the differences in toxicity and interaction responses of C. pyrenoidosa to antidepressants and their ternary mixture designed by the uniform design ray method. The toxic effects of individual antidepressants and their mixtures on C. pyrenoidosa were systematically investigated by the time-dependent microplate toxicity analysis (t-MTA) method. Toxicity interactions (synergism or antagonism) within mixtures were analyzed by the concentration addition (CA) and the deviation from the CA model (dCA) models. The results showed that the toxicities of the three antidepressants were different, and the order was FLU > APC > CIT. Light-dark cycles obviously affect the toxicity of three antidepressants and their combined toxicity interaction. Toxicity of the three antidepressants increases with the duration of light but decreases with the duration of darkness. The ternary antidepressant mixture exhibits antagonism, and the longer the initial lighting is, the stronger the antagonism. The antagonism of the ternary mixture is also affected by exposure time and mixture components' pi as well as exposure concentration.

Molecular Absorption Scanning and Assay of Serotonin Reception Inhibitor Antidepressant Drugs

Background:: Spectrophotometric techniques are based on the absorption of electromagnetic energy by the molecules of the substance analyzed and can be applied to drug analysis. Objective:: This study has been proposed to carry out molecular absorption scanning and assay in the ultraviolet region of generic antidepressant drugs of the serotonin reuptake inhibitor class produced by three Brazilian laboratories, addressing the importance of good manufacturing practices, drug quality control, and the use of qualitative and quantitative analytical techniques. Methods:: The physicochemical analyses were performed in a Marte Científica (580 UVP) UV-Vis spectrophotometer, and the result was evaluated according to the acceptance interval described in the Brazilian Pharmacopoeia. Results:: When calculating the dosage of the fluoxetine hydrochloride sample, the value of 90.95% was obtained and, therefore, the drug was approved for the dosage test. The dosage test for the drugs, citalopram hydrobromide and sertraline hydrochloride, was also approved, obtaining values of 102.4% and 98.2%, respectively. Conclusion:: The results presented provide future perspectives regarding the rigor of the need for good drug handling practices, maintenance and qualification of quality control laboratory equipment, and the guarantee of validation of analytical methodologies used in the pharmaceutical industries, contributing to the improvement of the quality of production and pharmaceutical products analysis.

Olfactory-Related Adverse Events: An Analysis of the Food and Drug Administration Adverse Events Reporting System.

Olfactory dysfunction has gained considerable interest with its association to the coronavirus pandemic. Due to the limited literature on olfactory-related adverse events (ORAE) associated with medications, this study investigated ORAE reported in the Food and Drug Administration Adverse Event Reporting System (FAERS) to identify the most frequent medications associated with these reactions. Cross-sectional analysis SETTING: FAERS database. The FAERS database was accessed to obtain ORAEs from 2012 to 2022. Disproportionality analysis was conducted by calculating the proportional reporting ratios (PRR) and reporting odds ratio (ROR) for anosmia, parosmia, hyposmia, and olfactory dysfunction. A PRR > 2 or ROR > 1 was significant. A multivariate logistical model was used to estimate adjusted ROR for gender and country of origin. Our final study population consisted of 1111 cases with the following symptoms: anosmia (672), parosmia (364), hyposmia (71), and olfactory dysfunction (4). The most significant ROR signal scores were found for secukinumab (3.42; 95% confidence interval, CI [1.9, 4.01]) for anosmia, levofloxacin (8.86; 95% CI [2.83, 9.8]) for hyposmia, and pregabalin (6.88; 95% CI [2.23, 8.01]) for parosmia. No significant PRR signal scores were found for anosmia, but significant signals were found for citalopram hydrobromide (17.25; 95% CI [17.01, 17.49]) in hyposmia, and dimethyl fumarate (3.18; 95% CI [3.09, 3.27]) in parosmia. No valid PRR or ROR values were found for olfactory dysfunction. Multivariate analysis did not reveal statistically significant differences between genders for any symptoms, but individuals from non-US countries did exhibit statistically significant elevated risk of anosmia (1.3 (95% CI [1.01, 1.68]). Pharmacovigilance studies provide an opportunity to evaluate the safety profile of medications regarding ORAE, particularly for those commonly prescribed for sinonasal symptoms. Findings from this study may function as a resource for prescribers and patients.

Enhanced removal of emerging pollutants through visible light-activated carbon nitride materials immobilized over 3D printed structures

This study investigates the performance of carbon nitride (CN) photocatalysts immobilized on 3D printed cylindrical supports for the removal of selected emerging pollutants, namely venlafaxine (VFX), citalopram (CTP), fluoxetine (FXT), and carbamazepine (CBZ), due to their rising consumption as antidepressants and the significant concerns for public health and the environment, mainly due to the direct impact of their presence in surface waters. The CN photocatalysts were synthesized using two precursors (dicyandiamide and urea), forming four different CN materials. Among the immobilized CN photocatalysts tested, the bulk CN prepared from urea (CNB-U/PLA) revealed the highest efficiency for the removal of VFX as the target antidepressant (above 90% after 30 min), which was ascribed to the lower recombination of photogenerated charges of this photocatalyst. The reuse tests confirmed the robust and effective photocatalytic performance of the CNB-U/PLA photocatalyst over multiple cycles, while its versatility with different support configurations demonstrates its adaptability and broad potential for various photocatalytic applications. The simultaneous removal of the four antidepressants was performed at low concentrations (1.8 μM), employing the most efficient immobilized photocatalyst (CNB-U/PLA), yielding remarkably high conversion rates (above 90% for VFX, CTP, and FXT, and around 70% for CBZ, after 60 min) under visible irradiation. The results demonstrate the ability of the immobilized CN system to effectively eliminate contaminants with different chemical properties. This study emphasizes the potential of this approach for comprehensive emerging pollutants removal, highlighting its significance in water treatment and environmental remediation strategies.

Antidepressant-like effects of the Punica granatum and citalopram combination are associated with structural changes in dendritic spines of granule cells in the dentate gyrus of rats.

Introduction: Natural products such as phytoestrogens-enriched foods or supplements have been considered as an alternative therapy to reduce depressive symptoms associated with menopause. It is known that the aqueous extract of Punica granatum (AE-PG) exerts antidepressant-like effects by activating β-estrogen receptors and facilitates the antidepressant response of the clinical drug citalopram (CIT). However, the effects on neuroplasticity are unknown. Objectvie investigated the antidepressant-like response of combining AE-PG and CIT at sub-optimal doses, analyzing their effects on the formation and maturation of dendrite spines in granule cells as well as on the dendrite complexity. Methods: Ovariectomized Wistar rats (3-month-old) were randomly assigned to one of the following groups: A) control (saline solution as vehicle of CIT and AE-PG, B) AE-PG at a sub-threshold dose (vehicle of CIT plus AE-PG at 0.125mg/kg), C) CIT at a sub-threshold dose (0.77mg/kg plus vehicle of AE-PG), and D) a combination of CIT plus AE-PG (0.125mg/kg and 0.77mg/kg, respectively). All rats were treated intraperitoneally for 14 days. Antidepressant-like effects were evaluated using the force swimming test test (FST). The complexity of dendrites and the number and morphology of dendrite spines of neurons were assessed in the dentate gyrus after Golgi-Cox impregnation. The expressions of the mature brain-derived neurotrophic factor (mBDNF) in plasma and of mBDNF and synaptophysin in the hippocampus, as markers of synaptogenesis, were also determined. Results: Administration of CIT combined with AE-PG, but not alone, induced a significant antidepressant-like effect in the FST with an increase in the dendritic complexity and the number of dendritic spines in the dentate gyrus (DG) of the hippocampus, revealed by the thin and stubby categories of neurons at the granular cell layer. At the same time, an increase of mBDNF and synaptophysin expression was observed in the hippocampus of rats that received the combination of AE-PG and CIT.

Utility of vitamin C in ameliorating citalopram-induced testicular toxicity via modulating nitro-oxidative stress and apoptosis in mice.

There is a growing concern that antidepressant drugs impair sexual function and adversely impact spermatogenesis and male fertility. Vitamin C is a natural antioxidant that plays a vital role in the male reproductive system. The present study investigated the ameliorating potential of vitamin C against citalopram (CTL)-evoked testicular toxicity and spermatogenesis impairment in mice. Mice were randomly divided into six groups: control, CTL, vitamin C 100, vitamin C 200, CTL plus vitamin C 100, and CTL plus vitamin C 200. Adult male mice were intraperitoneally (ip) injected with 10 mg/kg of CTL for 35 days with or without vitamin C. At the end of the study, body and testes weight, sperm parameters, histopathology of testes, testosterone level, testicular levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), and apoptosis (TUNEL assay) were evaluated. Our findings revealed that vitamin C restored spermatogenesis by improving sperm count, motility, viability, morphology, and chromatin integrity. Testosterone levels and testes histopathology were significantly improved in the vitamin C-administrated groups. Furthermore, vitamin C administration markedly alleviated CTL-induced nitro-oxidative damage, enhancing TAC levels, and reducing NO and MDA levels. Whilst CTL therapy induced a significant increase in the number of TUNEL-positive cells compared to the control, the administration of vitamin C significantly prevented the apoptotic effects of CTL. Together, vitamin C therapy protects against CTL-induced testicular damage via mitigating nitro-oxidative stress and apoptosis, which provides evidence for vitamin C as a beneficial therapy against antidepressant drug-associated reproductive toxicity and male sub/infertility.

Toward Personalized Treatment of Depression: An Affordable Citalopram Test based on a Solid-Contact Potentiometric Electrode for at-Home Monitoring of the Antidepressant Dosage.

Citalopram (CTLP) is one of the most common antidepressants prescribed worldwide. It has a narrow therapeutic window and can cause severe toxicity and mortality if the dosage exceeds the safe level. Reports indicated that at-home monitoring of citalopram dosage considerably benefits the patients, yet there are no devices capable of such measurement of citalopram in biofluids. This work presents an affordable citalopram test for at-home and point-of-care monitoring of citalopram levels in urine, ensuring a safe and effective drug compliance. Our platform consists of a citalopram-selective yarn-based electrode (CTLP-SYE) that uses polymeric sensing membranes to provide valuable information about drug concentration in urine. CTLP-SYE is noninvasive and has a response time of fewer than 10 s. The fabricated electrode showed near-Nernstian behavior with a 52.3 mV/decade slope in citalopram hydrobromide solutions ranging from 0.5 μM to 1.0 mM, with a detection limit of 0.2 μM. Results also indicated that neither interfering ions nor pH affects electrode performance. We showed that CTLP-SYE could accurately and reproducibly measure citalopram in human urine (RSD 2.0 to 3.2%, error <12%) at clinically relevant concentrations. This work paves the way for the personalized treatment of depression and accessible companion diagnostics to improve treatment efficacy and safety.

The atypical antidepressant tianeptine confers neuroprotection against oxygen–glucose deprivation

Proregenerative and neuroprotective effects of antidepressants are an important topic of inquiry in neuropsychiatric research. Oxygen–glucose deprivation (OGD) mimics key aspects of ischemic injury in vitro. Here, we studied the effects of 24-h pretreatment with serotonin (5-HT), citalopram (CIT), fluoxetine (FLU), and tianeptine (TIA) on primary mouse cortical neurons subjected to transient OGD. 5-HT (50 μM) significantly enhanced neuron viability as measured by MTT assay and reduced cell death and LDH release. CIT (10 μM) and FLU (1 μM) did not increase the effects of 5-HT and neither antidepressant conferred neuroprotection in the absence of supplemental 5-HT in serum-free cell culture medium. By contrast, pre-treatment with TIA (10 μM) resulted in robust neuroprotection, even in the absence of 5-HT. Furthermore, TIA inhibited mRNA transcription of candidate genes related to cell death and hypoxia and attenuated lipid peroxidation, a hallmark of neuronal injury. Finally, deep RNA sequencing of primary neurons subjected to OGD demonstrated that OGD induces many pathways relating to cell survival, the inflammation-immune response, synaptic dysregulation and apoptosis, and that TIA pretreatment counteracted these effects of OGD. In conclusion, this study highlights the comparative strength of the 5-HT independent neuroprotective effects of TIA and identifies the molecular pathways involved.

Computational Study of Photodegradation Process and Conversion Products of the Antidepressant Citalopram in Water.

Citalopram (CIT) is a commonly prescribed medication for depression. However, the photodegradation mechanism of CIT has not yet been fully analyzed. Therefore, the photodegradation process of CIT in water is studied by density functional theory and time-dependent density functional theory. The calculated results show that during the indirect photodegradation process, the indirect photodegradation of CIT with ·OH occurs via OH-addition and F-substitution. The minimum activation energy of C10 site was 0.4 kcal/mol. All OH-addition and F-substitution reactions are exothermic. The reaction of 1O2 with CIT includes the substitution of 1O2 for F and an addition reaction at the C14 site. The Ea value of this process is 1.7 kcal/mol, which is the lowest activation energy required for the reaction of 1O2 with CIT. C-C/C-N/C-F cleavage is involved in the direct photodegradation process. In the direct photodegradation of CIT, the activation energy of the C7-C16 cleavage reaction was the lowest, which was 12.5 kcal/mol. Analysis of the Ea values found that OH-addition and F-substitution, the substitution of 1O2 for F and addition at the C14 site, as well as the cleavage reactions of C6-F/C7-C16/C17-C18/C18-N/C19-N/C20-N are the main pathways of photodegradation of CIT.

Polyvinyl alcohol/citric acid/β-cyclodextrin/CuONP composite nanofibers as an effective and green absorbent for the simultaneous extraction of three antidepressant drugs in biological fluids prior to GC-FID analysis.

Composite nanofibers, namely, polyvinyl alcohol (PVA), citric acid (CA), β-cyclodextrin (β-CD), and copper oxide nanoparticles (PVA/CA/β-cyclodextrin/CuO NPs), were developed as a novel, green, and efficient adsorbent in the pipette tip-micro-solid-phase extraction method (PT-µSPE), for the simultaneous extraction of three antidepressants drugs namelyimipramine (IMP), citalopram (CIT), and clozapine (CLZ) in biological fluids before quantification by gas chromatography (GC-FID). Based on the obtained results from field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD), the successful synthesis of composite nanofibers was approved. Due to the presence of β-cyclodextrins and CuO NPs rich of functional groups on their surface, thenanofibers have high extraction efficiency. Under the optimal conditions, the linear range for imipramine, citalopram, and clozapine was 0.1 to 1000.0ngmL-1 with a determination coefficient ≥ 0.99. The limits of detection (LODs) were in the range0.03 to 0.15ngmL-1. The relative standard deviation was 4.8 to 8.7% (within-day, n = 4) and 5.1 to 9.2% (between-day, n = 3) for 3 consecutive days. In addition,excellent clean-up was achieved which is a great advantage over other sample preparation methods. Finally, the ability of the developed method to extract the target analytes from the biological samples was evaluated.