Citalopram exposure of hESCs during neuronal differentiation identifies dysregulated genes involved in neurodevelopment and depression.

Selective serotonin reuptake inhibitors (SSRIs), including citalopram, are widely used antidepressants during pregnancy. However, the effects of prenatal exposure to citalopram on neurodevelopment remain poorly understood. We aimed to investigate the impact of citalopram exposure on early neuronal differentiation of human embryonic stem cells using a multi-omics approach. Citalopram induced time- and dose-dependent effects on gene expression and DNA methylation of genes involved in neurodevelopmental processes or linked to depression, such as BDNF, GDF11, CCL2, STC1, DDIT4 and GAD2. Single-cell RNA-sequencing analysis revealed distinct clusters of stem cells, neuronal progenitors and neuroblasts, where exposure to citalopram subtly influenced progenitor subtypes. Pseudotemporal analysis showed enhanced neuronal differentiation. Our findings suggest that citalopram exposure during early neuronal differentiation influences gene expression patterns associated with neurodevelopment and depression, providing insights into its potential neurodevelopmental impact and highlighting the importance of further research to understand the long-term consequences of prenatal SSRI exposure.

Escitalopram moderately outperforms citalopram towards anti-neuroinflammation and neuroprotection in 6-hydroxydopamine-induced mouse model of Parkinson's disease.

Citalopram and escitalopram are structurally close-related antidepressants and both forms are widely used in the world. We aimed to comparatively evaluate the anti-neuroinflammatory and neuroprotective effects of escitalopram and citalopram in Parkinson's disease (PD) mouse model. Mice were randomly divided into six groups and received 6-hydroxydopamine (6-OHDA) or vehicle administration. The mice were then treated with escitalopram, citalopram or saline for consecutive 7 days. Behaviors, neuroinflammation, neurotransmitters, and neurotoxicity were assessed. Results showed that citalopram but not escitalopram worsened body weight loss and increased freezing time in the PD mice. Both drugs had no impact on the anxiety-like behaviors but ameliorated the depressive-like behaviors as in elevated plus maze and sucrose splash tests. Escitalopram but not citalopram ameliorated motor discoordination in the PD mice as in rotarod test. In accordance, escitalopram but not citalopram attenuated the 6-OHDA-induced nigrostriatal dopaminergic loss. Further mechanistic investigations showed that both drugs mitigated activations of microglia and astrocytes and/or levels of pro-inflammatory cytokines in the PD mice, but escitalopram showed appreciably better effects in the substantia nigra. Neurotransmitter examination in the prefrontal cortex suggested that the two drugs had comparable effects on the disturbed neurotransmitters in the PD mice, but citalopram was prone to disrupt certain normal homeostasis. In conclusion, escitalopram is moderately superior than citalopram to suppress neuroinflammation and to protect against dopaminergic neuronal death and motor discoordination in the 6-OHDA-induced PD mice. Our findings imply that escitalopram shall be prescribed with priority over citalopram to treat PD patients with depression as escitalopram may meanwhile provide greater additional benefits to the patients.

An Unexpected Phenomenon: A Case of Citalopram-Induced Dyskinesia.

Dyskinetic movements are characterized as hyperkinetic, repetitive movements of the extremities, facial, and oral musculature, most associated with prolonged dopamine D2 receptor blockade. In rare instances, dyskinetic movements can be brought on by selective serotonin reuptake inhibitor (SSRI) usage via an indirect D2 blockade mechanism, mimicking the D2 blockade observed with dopamine receptor blocking agents (DRBAs), such as in first-generation antipsychotics. This mimicked D2 blockade by SSRIs is said to be due to increased tonic inhibition by serotonin on dopaminergic neurons in the dopaminergic pathways of the brain, specifically the nigrostriatal pathway. In this case report, we look at a patient with a history of cerebral palsy who developed acute dyskinetic movements after short-term citalopram usage. The objective is to bring attention to the possible extrapyramidal side effects (EPS) of SSRI usage.

Effects of selective serotonin reuptake inhibitors on endocrine system (Review).

Selective serotonin reuptake inhibitors (SSRIs) are typically prescribed for treating major depressive disorder (MDD) due to their high efficacy. These drugs function by inhibiting the reuptake of serotonin [also termed 5-hydroxytryptamine (5-HT)], which raises the levels of 5-HT in the synaptic cleft, leading to prolonged activation of postsynaptic 5-HT receptors. Despite the therapeutic benefits of SSRIs, this mechanism of action also disturbs the neuroendocrine response. Hypothalamic-pituitary-adrenal (HPA) axis activity is strongly linked to both MDD and the response to antidepressants, owing to the intricate interplay within the serotonergic system, which regulates feeding, water intake, sexual drive, reproduction and circadian rhythms. The aim of the present review was to provide up-to-date evidence for the proposed effects of SSRIs, such as fluoxetine, citalopram, escitalopram, paroxetine, sertraline and fluvoxamine, on the endocrine system. For this purpose, the literature related to the effects of SSRIs on the endocrine system was searched using the PubMed database. According to the available literature, SSRIs may have an adverse effect on glucose metabolism, sexual function and fertility by dysregulating the function of the HPA axis, pancreas and gonads. Therefore, considering that SSRIs are often prescribed for extended periods, it is crucial to monitor the patient closely with particular attention to the function of the endocrine system.

Effect of reboxetine and citalopram on anal opening pressure in healthy women: A randomized, double-blind, placebo-controlled crossover study.

BACKGROUND: In placebo-controlled clinical trials, reboxetine, a selective noradrenaline reuptake inhibitor, increases urethral pressure and relieves stress urinary incontinence symptoms in women. Considering the close connection in neural regulation of the external urethral and anal sphincters, we hypothesized that reboxetine may also enhance anal sphincter pressure. Conversely, it is believed that selective serotonin reuptake inhibitors may contribute to fecal incontinence by reducing anal sphincter pressure. In this study, we investigated the effect of reboxetine and citalopram on anal opening pressure in healthy female volunteers. METHODS: In a double-blind, three-way crossover trial, 24 female participants received single doses of 40 mg citalopram, 8 mg reboxetine, and matching placebos, with a minimum of 8-day washout between sessions. Using anal acoustic reflectometry, we measured anal opening pressure during both resting and squeezing conditions at the estimated time of peak plasma concentration for both study drugs. KEY RESULTS: Compared with placebo, reboxetine increased anal opening pressure with 23.4 cmH2O (95% confidence interval [CI] 16.5-30.2, p < 0.001) during rest and with 22.5 cmH2O (95% CI 15.2-29.8, p < 0.001) during squeeze. Citalopram did not change anal opening pressure statistically significantly compared to placebo. CONCLUSIONS & INFERENCES: An 8-mg dose of reboxetine increased anal opening pressure substantially in healthy women, suggesting potential benefits for fecal incontinence symptoms. In contrast, a 40-mg dose of citalopram showed a marginal and statistically insignificant effect on anal opening pressure, indicating that selective serotonin reuptake inhibitors do not contribute to fecal incontinence by reducing anal sphincter tone.

Citalopram-Induced Oral Melanotic Macules in a Female Patient and a Review of the Literature.

Pigmented lesions in the oral cavity can arise from the accumulation of external substances or internal pigments, resulting in black or brown discoloration. The etiology can be categorized as physiologic, reactive, neoplastic, idiopathic, or indicative of systemic illness. Several systemic drugs have been linked to the development of oral and/or cutaneous pigmentation, either by stimulating the production of melanin or by the accumulation of the drug or its byproducts. The medications most commonly associated with this condition include antimalarials, hormones, oral contraceptives, phenothiazines, chemotherapeutics, amiodarone, minocycline, zidovudine, clofazimine, and ketoconazole. The aim of this case report is to illustrate the drug-induced appearance of multiple melanotic macules in an 89-year-old female patient. The patient was referred to the Department of Oral Medicine and Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, complaining of the recent and constant appearance of black spots in her oral cavity. Her medical history revealed a multitude of prescribed drugs, with citalopram being the most recently prescribed one, approximately one year prior to the examination. The clinical examination revealed multiple melanotic macules, on the upper and lower lip as well as on the hard and soft palate. Based on these findings, a biopsy of a melanotic macule of the lip was carried out. The histopathological examination showed that the basal layer of the stratified squamous epithelium exhibited hyperpigmentation (melanin-pigmented basal cells). In addition, scattered melaninophages were noted in lamina propria. Psychotropic drugs associated with cutaneous hyperpigmentation include citalopram. Therefore, our case constitutes an exception since citalopram induced intraoral and perioral, instead of cutaneous, hyperpigmentation.

Serotonergic Regulation of Synaptic Dopamine Levels Mitigates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease.

Background: The serotonin (5-HT) system can manipulate the processing of exogenous L-DOPA in the DA-denervated striatum, resulting in the modulation of L-DOPA-induced dyskinesia (LID). Objective: To characterize the effects of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) or the serotonin transporter (SERT) inhibitor, Citalopram on L-DOPA-induced behavior, neurochemical signals, and underlying protein expressions in an animal model of Parkinson's disease. Methods: MitoPark (MP) mice at 20 weeks of age, subjected to a 14-day administration of L-DOPA/Carbidopa, displayed dyskinesia, referred to as LID. Subsequent investigations explored the effects of 5-HT-modifying agents, such as 5-HTP and Citalopram, on abnormal involuntary movements (AIMs), locomotor activity, neurochemical signals, serotonin transporter activity, and protein expression in the DA-denervated striatum of LID MP mice. Results: 5-HTP exhibited duration-dependent suppressive effects on developing and established LID, especially related to abnormal limb movements observed in L-DOPA-primed MP mice. However, Citalopram, predominantly suppressed abnormal axial movement induced by L-DOPA in LID MP mice. We demonstrated that 5-HTP could decrease L-DOPA-upregulation of DA turnover rates while concurrently upregulating 5-HT metabolism. Additionally, 5-HTP was shown to reduce the expressions of p-ERK and p-DARPP-32 in the striatum of LID MP mice. The effect of Citalopram in alleviating LID development may be attributed to downregulation of SERT activity in the dorsal striatum of LID MP mice. Conclusions: While both single injection of 5-HTP and Citalopram effectively mitigated the development of LID, the difference in mitigation of AIM subtypes may be linked to the unique effects of these two serotonergic agents on L-DOPA-derived DA and 5-HT metabolism.

Design and synthesis of S-citalopram-imprinted polymeric sorbent: Characterization and application in enantioselective separation.

The current work describes the efficient creation and employment of a new S-citalopram selective polymeric sorbent, made from poly(divinylbenzene-maleic anhydride-styrene). The process began by using suspension polymerization technique in the synthesis of poly(styrene-maleic anhydride-divinylbenzene) microparticles. These were then modified with ethylenediamine, developing an amido-succinic acid-based polymer derivative. The S-citalopram, a cationic molecule, was loaded onto these developed anionic polymer particles. Subsequently, the particles were post-crosslinked using glyoxal, which reacts with the amino group residues of ethylenediamine. S-citalopram was extracted from this matrix using an acidic solution, which also left behind stereo-selective cavities in the S-citalopram imprinted polymer, allowing for the selective re-adsorption of S-citalopram. The attributes of the polymer were examined through methods such as 13C NMR, FTIR, thermogravemetric and elemental analyses. SEM was used to observe the shapes and structures of the particles. The imprinted polymers demonstrated a significant ability to adsorb S-citalopram, achieving a capacity of 878 mmol/g at a preferred pH level of 8. It proved efficient in separating enantiomers of (±)-citalopram via column methods, achieving an enantiomeric purity of 97 % for R-citalopram upon introduction and 92 % for S-citalopram upon release.

Methylphenidate, but not citalopram, decreases impulsive choice in rats performing a temporal discounting task.

Introduction: Drugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs affecting serotonin reuptake and dopamine reuptake can modulate distinct aspects of impulsivity - though such tests are often performed using distinct behavioral tasks prohibiting easy comparisons. Methods: Here, we directly compare pharmacologic agents that affect dopamine (methylphenidate) vs serotonin (citalopram) manipulations on choice impulsivity in a temporal discounting task where rats could choose between a small, immediate reward or a large reward delayed at either 2 or 10s. In control conditions, rats preferred the large reward at a small (2s) delay and discounted the large reward at a long (10s) delay. Results: Methylphenidate, a dopamine transport inhibitor that blocks reuptake of dopamine, dose-dependently increased large reward preference in the long delay (10s) block. Citalopram, a selective serotonin reuptake inhibitor, had no effect on temporal discounting behavior. Impulsive behavior on the temporal discounting task was at least partially mediated by the nucleus accumbens shell. Bilateral lesions to the nucleus accumbens shell reduced choice impulsivity during the long delay (10s) block. Following lesions, methylphenidate did not impact impulsivity. Discussion: Our results suggest that striatal dopaminergic systems modulate choice impulsivity via actions within the nucleus accumbens shell, whereas serotonin systems may regulate different aspects of behavioral inhibition/impulsivity.

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 (0.5-23.8 mg). 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.

The Importance of Including Variable Exposure Concentrations When Assessing Toxicity of Sediment-Associated Pharmaceuticals to an Amphipod.

Pharmaceuticals have been classified as an environmental concern due to their increasing consumption globally and potential environmental impact. We examined the toxicity of sediment-associated diclofenac and citalopram administered as both single compounds and in a mixture to the sediment-living amphipod Corophium volutator. This laboratory-based study addressed the following research questions: (1) What is the toxicity of sediment-associated diclofenac and citalopram to C. volutator? (2) Can the mixture effect be described with either of the two mixture models: concentration addition (CA) or independent action (IA)? (3) What is the importance of the choice of (i) exposure measure (start concentration, time-weighted average [TWA], full exposure profile) and (ii) effect model (concentration-response vs. the toxicokinetic-toxicodynamic model general unified threshold model for survival in its reduced form [GUTS-RED]) for the derived effect concentration values? Diclofenac was more toxic than citalopram to C. volutator as a single compound (10-day exposure). Diclofenac exposure to C. volutator provided median lethal concentrations (LC50s) within the same range (11 µg g-1 dry wt sediment) using concentration-response based on TWA and both GUTS-RED models. However, concentration-response based on measured start concentrations provided an approximately 90% higher LC50 (21.6 ± 2.0 µg g-1 dry wt sediment). For citalopram, concentration-response parameters were similar regardless of model or concentration used (LC50 85-97 µg g-1 dry wt sediment), however, GUTS-RED with the assumption of individual tolerance resulted in a lower LC50 (64.9 [55.3-74.8] µg g-1 dry wt sediment). The mixture of diclofenac and citalopram followed the CA quite closely, whereas the result was synergistic when using the IA prediction. In summary, concentration-response based on TWA and GUTS-RED provided similar and reasonably good fits compared to the data set. The implications are that GUTS-RED will provide a more flexible model, which, in principle, can extend beyond the experimental period and make predictions based on variable exposure profiles (toxicity at different time frames and at different variable exposure scenarios) compared to concentration-response, which provides contaminant toxicity at one point in time. Environ Toxicol Chem 2024;43:1767-1777. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Citalopram, an antipsychotic agent, induces G1/G0 phase cell cycle arrest and promotes apoptosis in human laryngeal carcinoma HEP-2 cells.

Human laryngeal squamous carcinoma (LSCC) is a common malignant tumor in the head and neck. Despite the recently developed therapies for the treatment of LSCC, patients' overall survival rate still did not enhance remarkably; this highlights the need to formulate alternative strategies to develop novel treatments. The antitumor effects of antidepressant drugs such as citalopram have been reported on several cancer cells; however, they have yet to be investigated against LSCC. The current study was directed to explore the possible antitumor effects of citalopram on human laryngeal carcinoma cell lines (HEP-2). HEP-2 cells were cultured and treated with different doses of citalopram (50-400 µM) for 24, 48, and 72 h. The effects of citalopram on the viability of cancer cells were determined by the MTT assay. In addition, apoptosis and cell cycle analysis were performed by flow cytometry. Moreover, evaluation of the expression of proapoptotic and apoptotic proteins, such as cytochrome c, cleaved caspases 3 and 9, Bcl-2, and BAX, was performed by western blotting analysis. Our results revealed that citalopram significantly suppressed the proliferation of HEP-2 cells through the upregulation of p21 expression, resulting in the subsequent arrest of the cell cycle at the G0/G1 phase. Furthermore, citalopram treatment-induced HEP-2 cell apoptosis; this was indicated by the significant increase of cytochrome c, cleaved caspases 3 and 9, and BAX protein expression. On the contrary, Bcl-2 protein expression was significantly downregulated following treatment with citalopram. The ultrastructure studies were in accordance with the protein expression findings and showed clear signs of apoptosis with ring chromatin condensation upon treatment with citalopram. These findings suggest that citalopram's anti-tumor activities on HEP-2 cells entailed stimulation of the intrinsic apoptotic pathway, which was mediated via Bcl-2 suppression.

Interaction effect of crocin and citalopram on memory and locomotor activity in rats: an insight into BDNF and synaptophysin levels in the hippocampus.

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for the treatment of depression. Citalopram is one of the most prescribed SSRIs that is useful for the treatment of depression, obsessive-compulsive disorder, and anxiety disorders. On the other hand, crocin (active constitute of saffron) has pro-cognitive and mood enhancer effects. Also, both citalopram and crocin affect the function and expression of brain-derived neurotrophic factor (BDNF) and synaptophysin, two molecular factors that are involved in cognitive functions and mood. In the present study, we aim to investigate the interaction effect of citalopram and crocin on rats' performance in the open field test (locomotor activity and anxiety-like behavior) and the shuttle box (passive avoidance memory). Citalopram was injected at the doses of 10, 30, and 50 mg/kg, and crocin was injected at the dose of 50 mg/kg; all administrations were intraperitoneal. Real-time PCR was used to assess the expression level of BDNF and synaptophysin in the hippocampus. The results showed that citalopram (30 and 50 mg/kg) impaired passive avoidance memory and decreased BDNF and synaptophysin expression in the hippocampus, while crocin reversed memory impairment, and BDNF and synaptophysin expression in the hippocampus of rats received citalopram 30 mg/kg. Also, crocin partially showed these effects in rats that received citalopram 50 mg/kg. The results of the open field test were unchanged. In conclusion, we suggested that BDNF and synaptophysin may be involved in the effects of both citalopram and crocin.

Effects of citalopram on blood pressure control in depressive patients with hypertension: A randomized clinical trial.

Introduction: Since there is a bi-directional interaction between hypertension and depression, we aimed to evaluate the effects of citalopram administration in the management of hypertension. Methods: A randomized clinical trial was conducted on 72 patients with concomitant depression and hypertension. The intervention group (n=41) received citalopram 20 mg daily plus anti-hypertensive standard treatment, while the control group (n=31) received only the standard treatment. The study's primary endpoint was in-office blood pressure (BP) measurement at baseline and home BP monitoring in the first and second months after entering the study. Results: There were no significant differences in baseline systolic BP (163.3±19.6 vs.164.2±20.3 mm Hg; P=0.910) and diastolic BP (94.5±13.8 vs. 88.2±14.4; P=0.071). After one month, diastolic BP (82.7±11.7 vs. 77.09±12.2; P=0.023) was significantly higher in the control group compared to the intervention group. Two months after the intervention, systolic BP (133.8±16.5 vs. 124.5±12.4; P=0.009) and diastolic BP (80.7±10.3 vs. 73.7±9.7; P=0.002) were significantly decreased in the intervention group compared to the control group. Conclusion: This study supported the beneficial effects of citalopram in lowering BP in patients with concomitant depression and hypertension.

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.

Sensitive, reliable and simultaneous determination of Fingolimod and Citalopram drug molecules used in multiple sclerosis treatment based on magnetic solid phase extraction and HPLC-PDA.

An analytical methodology has been developed for trace amounts of Fingolimod (FIN) and Citalopram (CIT) drug molecules based on magnetic solid phase extraction (MSPE) and high performance liquid chromatographic determination with photodiode array detector (HPLC-DAD). Fingolimod is used in treatment of Multiple sclerosis (MS) disease and sometimes antidepressant drugs such as citalopram accompany to treatment. Both simultaneous analysis of these molecules and application of MSPE with a new adsorbent has been performed for first times. Fe3O4@L-Tyrosine magnetic particles has been synthetized and characterized as a new magnetic adsorbent. Experimental variables of MPSE were examined and optimized step by step such as pH, adsorption and desorption conditions, time effect, etc. Analytical parameters of the proposed method were studied and determined under optimized conditions according to international guidelines. HPLC analysis of FIN and CIT molecules was performed by isocratic elution of a mixture of 50 % Acetonitrile, 40 % pH:3 phosphate buffer and 10 % methanol with flow rate 1.0 mL min-1. The chosen wavelengths in PDA was determined as 238 nm for FIN and 213 nm for CIT. The limits of detection (LOD) for proposed method were 6.32 ng mL-1 for FIN and 6.85 ng mL-1 for CIT molecules. RSD % values were lower than 5.5 % in analysis of model solutions including 250 and 500 ng mL-1 of target molecules. Recovery values by means of synthetic urine and saliva samples were in the range of 95.7-105.4 % for both molecules.

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.

Interaction between citalopram and omega-3 fatty acids on anxiety and depression behaviors and maintaining the stability of brain pyramidal neurons in mice.

This research was done to examine the combination of citalopram, an antidepressant drug, and omega-3 in a mice model of depression. Mice received citalopram (1 and 2 mg/kg) or omega-3 (10 and 20 mg/kg) daily over 30 days. Then, they were exposed to acute and chronic restraint stress to assess the possible increasing effect of omega-3 on the antidepressant and anxiolytic effects of citalopram. Elevated plus-maze (EPM) and forced swimming test (FST) were used to assess anxiety and depression symptoms in non-restraint stress (NRS), acute restraint stress (ARS), and chronic restraint stress (CRS) mice. The results indicated that induction of acute and chronic restraint stress reduced %OAT (Open arm time) and %OAE (Open arm entrance) in the EPM test but enhanced immobility time in the FST, showing anxiogenic- and depressive-like effects. These stresses reduced the stability of pyramidal neurons in the prefrontal cortex (PFC) and hippocampus. Aone and combination administration with citalopram and omega-3 induced anxiolytic- and antidepressant-like effects in NRS, ARS, and CRS mice. This combination usage increased the stability of pyramidal neurons in the PFC and hippocampus. These results suggested an interaction between citalopram and omega-3 upon the induction of anxiolytic- and antidepressant-like effects as well as augmentation of the ratio of pyramidal live to dark neurons in the PFC and hippocampus of the ARS and CRS mice.

Synergistic effect between citalopram and muscimol upon induction of anxiolytic- and antidepressant-like effects in male mice: An isobologram analysis.

Background: There is evidence that both the GABAergic system and serotonin reuptake inhibitor (SSRI) such as citalopram are involved in the modulation of anxiety and depression processes. In this research, we examined the effects of GABAA receptor agents and citalopram on anxiety- and depression-related behaviors and their interaction in male mice. Methods: For intracerebroventricular (i.c.v.) infusion, a guide cannula was implanted in the left lateral ventricle. Anxiety and depression behaviors were evaluated using the elevated plus-maze (EPM) and forced swimming test (FST). Results: The results revealed that i.c.v. microinjection of muscimol (1 µg/mouse) enhanced % OAT (open arm time) and % OAE (open arm entries) in the EPM test and decreased immobility time in the FST without affecting locomotor activity, presenting anxiolytic- and antidepressant-like behaviors in the EPM and FST, respectively. On the other hand, i.c.v. microinjection of bicuculline (1 µg/mouse) reduced % OAT and % OAE without affecting locomotor activity and immobility time, presenting an anxiogenic-like effect. Moreover, i.p. administration of citalopram (8 mg/kg) increased %OAT and %OAE and reduced immobility time with no effect on locomotor activity, showing anxiolytic- and antidepressant-like responses in male mice. Furthermore, i.c.v. infusion of an ineffective dosage of muscimol potentiated the anxiolytic- and antidepressant-like responses induced by i.p. injection of citalopram in male mice. When citalopram and bicuculline were co-injected, a non-significant dose of bicuculline reversed the anxiolytic-like effect of citalopram in male mice. Also, the data revealed synergistic anxiolytic- and antidepressant-like behaviors between citalopram and muscimol in male mice. Conclusions: The results suggested an interaction between citalopram and GABAergic agents on the modulation of anxiety and depression behaviors in male mice.