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Ulcerative colitis (UC) is an inflammatory bowel disease and psychological factors may be one of its pathogeneses. Selective serotonin reuptake inhibitor drug such as paroxetine with an effective anti‐depression ability may be a new option for UC treatment. To evaluate the therapeutic effect of paroxetine on the exacerbation of UC symptoms caused by depression, a dual model of C57BL/6 mice was established using dextran sulphate sodium and chronic unpredictable mild stress (CUMS). Behavioural experiments, H&E staining and the level of 5‐hydroxytryptamine (5‐HT) in the brain were used to demonstrate successful replication of the CUMS model. The levels of 5‐HT, TNF‐α and IL‐1β in the colon and the activity of MPO in the serum were determined by ELISA kits. The levels of some gut microbiota in the faeces were measured by qPCR and faecal differential metabolites were analysed by 1H NMR. The results indicate that CUMS can exacerbate UC symptoms in mice by exacerbating inflammation, and UC+CUMS can disrupt gut microbiota and fatty acid metabolism. Paroxetine can improve the mental state of mice, reduce serum MPO activity, but increase TNF‐α and IL‐1β levels in the colon. In addition, paroxetine also can restore the intestinal flora of mice and improve intestinal absorption and metabolic function of amino acids and short‐chain fatty acids. [ABSTRACT FROM AUTHOR]

Background: Post-myocardial infarction (MI) remodeling involves various structural and functional changes, such as inflammation and fibrosis. Upregulation of G protein-coupled receptor kinase 2 (GRK2) is linked to the progression of cardiovascular diseases, including myocardial infarction. The inhibitory effects of paroxetine on GRK2 are recognized, yet its protective effect on post-MI remodeling has not been elucidated. Here, we investigated the cardioprotective effect of paroxetine in an animal model of MI, focusing on post-MI cardiac remodeling and comparing its effect to a β-blocker and an angiotensin receptor antagonist. Methods: Albino Wistar rats were divided into five groups (control; untreated MI; and MI pre-treated with either paroxetine, metoprolol, or irbesartan). MI was induced using isoproterenol (100 mg.kg−1) on days 16 and 17. Cardioprotective effects were determined by assessing markers of cardiac injury, histopathology, inflammation, oxidative stress, and fibrosis. Statistical analysis performed using a one-way analysis of variance, followed by an appropriate post hoc test, the differences between the groups were considered significant when the (P < 0.05). Results: Paroxetine significantly attenuated cardiac injury biomarkers including serum Tn-I and CK-MB levels. In terms of cardiac remodeling, paroxetine significantly reduced the relative HW/BW index and the plasms FGF23 level. Furthermore, it modulated markers of fibrosis, inflammation, and oxidative stress. Conclusion: The current findings suggest that pre-treatment with paroxetine may exert a beneficial effect that protects against post-MI remodeling, including modulating fibrotic, inflammatory, and angiogenesis-related factors. Therefore, the current findings show the promising role of paroxetine as a cardioprotective that attenuates post-MI remodeling processes. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a common, debilitating condition with symptoms that cause substantial stress or functional impairment. Currently, paroxetine and sertraline are the only medications approved in the USA for the treatment of PTSD, but their efficacy is limited and there is an unmet need for new pharmacological options. Several pathophysiological pathways and processes of PTSD have been highlighted as targets for potential drug development, including brain hyper- and hypoactivity, the hypothalamic-pituitary-adrenal axis and the endocannabinoid system. The use of psychedelics in combination with psychotherapy are also being investigated for the treatment of PTSD. [ABSTRACT FROM AUTHOR]

Physicochemical properties, bioactivity scores, toxicity, chemical reactivity descriptor (GCRD), polarizability, and UV–vis spectroscopy of 10 common medicines used for the treatment of anxiety have been investigated to understand their activity and adverse effect in the human body. GCRD, polarizability, and UV–vis data of the drug molecules have been analyzed at the density functional M06‐2X/cc‐pVTZ level. Molinspiration, Osiris Property Explorer, and the SwissTargetPrediction tools have been used to study the molecular and physicochemical properties, drug likeness/bioactivity scores, and toxicity of the drug molecules. The calculated results show that all drug molecules have good bioavailability and are orally active, which corroborate with the clinical data. Most of the theoretical results are first reported, and the predicted results agree well with the clinical data and published reports wherever available. The calculated GCRD parameters confirm that chlordiazepoxide (D3) is the most reactive drug molecule. Drug likeness and drug score indicate that alprazolam (D1), chlordiazepoxide (D3), paroxetine (D7), and selegiline (D9) are safe medicines for humans. The predicted toxicities also substantiate the clinical data. The BOILED‐Egg plot illustrates that as alprazolam (D1) and paroxetine (D7) are the substrates of the P‐glycoprotein (PGP+), they are actively pumped up from the brain or to the gastrointestinal lumen. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have examined the correlation between paroxetine concentrations and therapeutic efficacy in patients diagnosed with major depressive disorder (MDD), but findings have been contradictory. Aims: This study aimed to investigate the relationships among plasma concentrations, severity of symptoms, and adverse drug reactions (ADRs) to optimize individual dosing. Methods: Eighty-seven MDD patients, after completing treatment with paroxetine, were divided into low-concentration (LC, n = 38), medium-concentration (MC, n = 27), and high-concentration (HC, n = 22) groups, based on cutoff value concentrations with the 50% response rate and the laboratory alert level from the 2017 consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology. The severity of depression and anxiety was evaluated using a 17-item Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA), respectively. Dosage, plasma concentrations, scale scores, and ADRs were recorded across the three groups at different treatment stages to define the therapeutic reference range. Results: The 4-week plasma concentration of paroxetine (65.00 ng/mL) could predict the clinical response in MDD patients at 8 weeks. Symptom relief in patients with 4-week paroxetine concentrations ranging from 65.00 to 120.00 ng/mL at 8 weeks was greater than in those with concentrations below 65.00 ng/mL, with no significant difference observed above this range. In addition, more cases of liver injury and weight gain were observed in patients with high paroxetine concentrations. Conclusion: Our results support that early paroxetine concentration may predict clinical efficacy and the incidence of ADRs, thus improving individual dosing regimens for MDD patients. [ABSTRACT FROM AUTHOR]

Compulsive sexual behavior disorder (CSBD) is a burgeoning diagnostic construct. No systematic reviews of CSBD pharmacotherapy interventions have been conducted. We addressed this gap using a three-aim approach. We reviewed researchers' theoretical arguments for various pharmacotherapies, outcomes from pharmacotherapy trials, and the generalizability of the extant findings. Our review included k = 13 studies, with n = 141 participants. An opioid model of reward seeking was the most popular framework, though inconsistently specified. A serotonin model was also documented, though with few details. Naltrexone was the most prominently examined pharmacotherapy and the only medication that reliably demonstrated a therapeutic effect for some (but not all) indicators compared to placebo. Paroxetine and citalopram were also documented in placebo-controlled trials, though their incremental benefit compared to placebo is suspect. Several additional pharmacotherapies have been documented in case series contexts. Across studies, only one female participant was identified. All trials were conducted in developed nations, and race was rarely assessed. We conclude that the case for pharmacotherapy for CSBD is limited and should preferably not occur outside of clinical trial contexts. Naltrexone offers the best evidence for a potential research program, though new theoretically informed approaches are welcome. Finally, we call for additional pharmacotherapy research in women and non-White populations. [ABSTRACT FROM AUTHOR]

This paper explores the development and characterization of epichlorohydrin-crosslinked β-cyclodextrin nanoparticles (βCDNPs) for drug delivery, focusing on their interaction with hydrophobic drugs and biocompatibility. We synthesized βCDNPs using β-cyclodextrin (βCD) and epichlorohydrin (ECH). Our study assessed the biocompatibility and safety of βCDNPs, particularly in avoiding nephrotoxicity commonly associated with βCD, by examining their interaction with cholesterol and conducting survival analyses in mice at various dosing concentrations. Additionally, we highlight the advantages of using diffusion-ordered NMR spectroscopy (DOSY) to determine the enhanced binding constants of βCDNPs with hydrophobic compounds, in comparison with the solubility method, Job plot analysis, and isothermal titration calorimetry (ITC). We demonstrated the enhanced binding capacity of βCDNPs compared to βCD alone and established the polymerization of βCD as a significant factor in this enhancement. Our findings suggest that βCDNPs show promise as drug delivery systems due to their improved solubility, stability, and safety profiles. [ABSTRACT FROM AUTHOR]

AbstractWe presented the results on the efficacy of paroxetine in postpartum women with generalized anxiety disorder (GAD) in current study. We included data on 33 patients to our study retrospectively. The patients were evaluated using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, the Clinical Global Impression-Improvement Scale, the Hamilton Depression rating Scale (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A). The patients had significant improvement in both HAM-D and HAM-A scores following paroxetine treatment for 8 wk. The response and remission rates were 78.8 and 63.6%, respectively. Both rates were significantly higher the subgroup of patients without comorbid depression compared to patients with comorbid depression. Based on the findings of the present study, we suggest that paroxetine may be beneficial for in postpartum women with GAD. [ABSTRACT FROM AUTHOR]

JC polyomavirus (JCPyV) infects the majority of the population and initially establishes a persistent but asymptomatic infection of the kidneys. In healthy individuals, the infection remains controlled by the host immune system, but for individuals experiencing prolonged immunosuppression, the infection can reactivate and spread to the brain, where it causes progressive multifocal leukoencephalopathy (PML), which is a fatal neurodegenerative disease. Currently, there are no approved therapies to treat PML, and affected individuals suffer rapid motor weakness and cognitive deterioration. To identify novel therapeutic treatments for JCPyV infection, receptor agonists/antagonists identified in a previously published drug screen were evaluated for their antiviral properties. Seven drugs were selected and validated using infectivity assays, and the mechanism of inhibition was further explored for G protein coupled receptor (GPCR)-associated inhibitors due to the role of the GPCR 5-hydroxytryptamine 2 receptors (5-HT2Rs) in JCPyV entry. The inhibitors cetirizine and paroxetine both reduced infection early in the JCPyV infectious cycle. Paroxetine specifically reduced viral internalization through altering the receptor density of 5-HT2CR, inhibiting β-arrestin recruitment to the receptor, and reducing MAPK signaling through ERK. These findings highlight the potential of receptor signaling and viral entry mechanisms as possible targets for antiviral drug development. Further, this research suggests that FDA-approved receptor agonists/antagonists currently used to treat other medical conditions could be repurposed into antivirals for the possible treatment of JCPyV infection and the fatal disease PML. [ABSTRACT FROM AUTHOR]

The aim of this study is to explore paroxetine's effect on nerve growth factor (NGF), human neurotrophin-4 (NT-4), and brain-derived neurotrophic factor (BDNF) levels in post-stroke depression. Ninety-two post-stroke depression patients from April 2021 to April 2023 in our hospital were selected and numbered 1 to 92 after enrollment. Forty-six patients with odd number and 46 patients with even number were, respectively, included in the control and observation group. In addition to basic treatment, control group was treated with flupentixol melitracen tablets orally, and observation group received paroxetine hydrochloride orally. The levels of NGF, NT-4, BDNF, 5-hydroxytryptamine (5-HT), homocysteine (Hcy), noradrenaline (NE), Hamilton Depression Scale (HAMD) changes of National Institute of Health Stroke Scale (NIHSS). NGF, NT-4, and BDNF levels were compared between groups at T0, T1, and T2 levels were higher, and the levels at T2 were higher than those at T1, and observation group levels were higher (P < 0.05); NGF, NT-4, and BDNF levels were compared among groups, time, and interaction. 5-HT, Hcy, and NE levels at T0 were compared between groups; 5-HT and NE levels at T1 and T2 were higher than those at T0, the levels at T2 were higher than those at T1, and observation group levels were higher (P < 0.05); Hcy level at T1 and T2 was lower, its level at T2 was lower than those at T1, and observation group levels were lower (P < 0.05); 5-HT, Hcy, and NE levels were compared among groups, time, and interaction (P < 0.05). HAMD and NIHSS at T0 were compared; T1 and T2 were lower than T0, T2 was lower than T1, and observation group was lower (P < 0.05); HAMD and NIHSS were compared among groups, time, and interaction (P < 0.05). For post-stroke depression, paroxetine treatment can effectively improve NGF, NT-4, BDNF, 5-HT, Hcy, and NE levels and effectively reduce the degree of neurological damage and depression, which has high clinical application value. [ABSTRACT FROM AUTHOR]

Objective: The cytochrome P450 2D6 (CYP2D6) is an enzyme involved in the oxidative biotransformation of various widely used drugs, including paroxetine, a substrate and strong inhibitor of the enzyme. The aim is to report on a case of protracted intoxication with paroxetine after a single overdose in a genotypepredicted intermediate CYP2D6 metabolizer. Observation: A 49-year-old man was receiving chronic treatment for more than 6 years with paroxetine 60 mg/day for an indication of agoraphobia. The patient ingested fifty 20 mg tablets of paroxetine in a suicide attempt. The toxic plasma level, accompanied by delirium, persisted for approximately 1 month after the overdose. According to the genotype profile, the patient was evaluated as an intermediate metabolizer with reduced CYP2D6 enzyme activity. Conclusion: As a consequence of the suicide attempt with overdose and the chronic paroxetine treatment that preceded it, phenoconversion to a poor metabolizer with very low CYP2D6 enzyme activity is suggested as contributing to an extremely long intoxication accompanied by delirium. Prolonged monitoring over a standard 24 h of both physical symptoms and drug plasma levels, together with a genetic profile assessment and phenoconversion consideration, is recommended after a single overdose in patients chronically treated with paroxetine. [ABSTRACT FROM AUTHOR]

Oyster peptide (OP) and Pfaffia glomerata extract (PGE) were used as raw materials. The optimal formulation of the pressed candy (PC) was optimized by one‐way experiment and D‐optimal mixture experiment design, and animal experiment was used to evaluate the effect of PC on male sexual dysfunction. The results showed that PC intervention significantly improved the sexual behavior of male mice with sexual dysfunction, including a significant shortening of the mount latency (ML) and intromission latency, and a significant increase in the mount frequency (MF) and intromission frequency (IF). At the same time, the concentrations of serum testosterone (T) and luteinizing hormone (LH) in mice were restored, and the erectile parameters and pathological changes of penile tissue were improved. Further studies found that PC intervention increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH‐Px) and reduced the content of malondialdehyde (MDA) in testicular tissue. In addition, PC intervention improved testicular tissue morphology. In conclusion, the obtained PC has good taste quality, and the relevant quality indicators are qualified. It has a good ameliorative effect on male sexual dysfunction and may be a potential dietary supplement. [ABSTRACT FROM AUTHOR]

IntroductionThis clinical trial is designed to explore the efficacy of paroxetine and gabapentin in alleviating functional gastrointestinal symptoms, anxiety, depression, and quality of life in patients with ulcerative colitis during the remission stage.MethodsThe study enrolled 97 patients with ulcerative colitis in remission who had reported functional gastrointestinal symptoms. Patients were measured in terms of quality of life, anxiety, depression, and IBS severity. One group received paroxetine at a dosage of 20 mg/day, and the other group received gabapentin at a dosage of 100 mg/day in the first month and 300 mg/day in the second and third months. The patients were followed up for 3 months.ResultsAnxiety (p < 0.001), depression (p = 0.012), and severity score levels (p = 0.045) among patients in the paroxetine group were significantly lower compared to the gabapentin group following the intervention. Paired evaluation in each treatment group revealed a significant reduction in the paroxetine group, while changes in the gabapentin group were not significant. Quality-of-life scores among patients in the paroxetine group were significantly higher compared to the gabapentin group following the intervention (p < 0.001).ConclusionThe rate of improvement in gastrointestinal functional symptoms, anxiety, depression, and quality of life is significantly superior with paroxetine compared to gabapentin.Clinical trial registrationhttps://irct.behdasht.gov.ir/trial/69397, identifier RCT20220417054557N1.

The article focuses on a study comparing weight gain risk across eight commonly used antidepressants, finding bupropion associated with the least weight gain and varying weight effects for other drugs over 6, 12, and 24 months.