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1.
Bioelectrochemistry ; 149: 108285, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36240548

RESUMO

This study is designed to investigate the interaction of phenylpiperidine derivative drug paroxetine, which is an effective serotonin reuptake inhibitor and biomolecules through electrochemical, fluorescence spectroscopy, and molecular docking methods. The interaction between paroxetine and biomolecules was investigated by differential pulse voltammetry according to the decrease in deoxyguanosine anodic oxidation signal of double-stranded calf thymus DNA. Fluorescence spectroscopy studies were performed by titrating paroxetine against double-stranded calf thymus DNA solution at four different temperatures. The fluorescent results showed that paroxetine had a great affinity to bind with double-stranded calf thymus DNA. Interaction studies demonstrate that paroxetine binds to double-stranded calf thymus DNA via intercalation binding mode, and the binding constant values ​​were calculated as 7.24 × 104 M-1 and 1.52 × 104 M-1 at 25 °C, based on voltammetric and spectroscopic results, respectively. Moreover, with the aim of elucidating the interaction mechanism between paroxetine and double-stranded calf thymus DNA, electrochemical and fluorescence spectroscopy studies along with molecular docking analysis were made.


Assuntos
DNA , Paroxetina , Antidepressivos/farmacologia , Dicroísmo Circular , DNA/química , Simulação de Acoplamento Molecular , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Termodinâmica
3.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6146-6154, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36471939

RESUMO

Since exploding rates of modern mental diseases, application of antidepressants has increased. Worryingly, the antidepressant-induced liver injury has gradually become a serious health burden. Furthermore, since most of the knowledge about antidepressant hepatotoxicity are from pharmacovigilance and clinical case reports and lack of observational studies, the underlying mechanisms are poorly understood and there is a lack of efficient treatment strategies. In this study, antidepressant paroxetine directly triggered inflammasome activation evidenced by caspase-1 activation and downstream effector cytokines interleukin(IL)-1ß secretion. The pretreatment of echinatin, a bioactive component of licorice, completely blocked the activation. This study also found that echinatin effectively inhibited the production of inflammasome-independent tumor necrosis factor α(TNF)-α induced by paroxetine. Mechanistically, the accumulation of mitochondrial reactive oxygen species(mtROS) was a key upstream event of paroxetine-induced inflammasome activation, which was dramatically inhibited by echinatin. In the lipopolysaccharide(LPS)-mediated idiosyncratic drug-induced liver injury(IDILI) model, the combination of LPS and paroxetine triggered aberrant activation of the inflammasome to induce idiosyncratic hepatotoxicity, which was reversed by echinatin pretreatment. Notably, this study also found that various bioactive components of licorice had an inhibitory effect on paroxetine-triggered inflammasome activation. Meanwhile, multiple antidepressant-induced aberrant activation of the inflammasome could be completely blocked by echinatin pretreatment. In conclusion, this study provides a novel insight for mechanism of antidepressant-induced liver injury and a new strategy for the treatment of antidepressant-induced hepatotoxicity.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Glycyrrhiza , Triterpenos , Humanos , Animais , Camundongos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Lipopolissacarídeos/toxicidade , Paroxetina/efeitos adversos , Interleucina-1beta , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Extratos Vegetais , Antidepressivos , Fator de Necrose Tumoral alfa , Camundongos Endogâmicos C57BL
4.
J. Health Biol. Sci. (Online) ; 10(1): 1-12, 01/jan./2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1382369

RESUMO

Objective: this systematic review aims to compile literature data on the antimicrobial action of Selective Serotonin Reuptake Inhibitors (SSRI). Methods: To this end, the articles in this review were searched in the PubMed database between the years 2010 to 2020, using terms found in MESH as descriptors. The PRISMA flow diagram was used to analyze the process flow of the research. Later, inclusion and exclusion criteria and eligibility for data extraction and statistical analysis were applied. Results: Thus, of 252 articles found, 13 were used for this systematic review. The period in which there were more publications was in 2016-2017. All articles demonstrated the antimicrobial activity of ISRS, such as sertraline, fluoxetine, and paroxetine, in addition to their synergistic activity with some antifungals and antibacterial. Conclusion: With this, it could be concluded that the repositioning of non-antibiotic drugs that have antimicrobial activity is a promising alternative for the scientific community and, in the future, in clinical practice


Objetivo: compilar dados da literatura sobre a ação antimicrobiana dos Inibidores Seletivos de Recaptação de Serotonina (ISRS). Métodos: os artigos desta revisão foram pesquisados na base de dados PubMed, entre os anos de 2010 a 2020, utilizando, como descritores, termos encontrados no MESH. O fluxograma PRISMA foi utilizado para analisar o fluxo do processo da pesquisa. Posteriormente, foram aplicados os critérios de inclusão e exclusão e de elegibilidade para extração de dados e análise estatística. Resultados: dos 252 artigos encontrados, 13 foram utilizados para esta revisão sistemática. O período em que houve mais publicações foi em 2016-2017. Todos os artigos demonstraram a atividade antimicrobiana do ISRS, como sertralina, fluoxetina e paroxetina, além de sua atividade sinérgica com alguns antifúngicos e antibacterianos. Conclusão: o reposicionamento de medicamentos não antibióticos que possuam atividade antimicrobiana é uma alternativa promissora para a comunidade científica e, futuramente, na prática clínica.


Assuntos
Inibidores de Captação de Serotonina , Antibacterianos , Antifúngicos , Bactérias , Serotonina , Fluoxetina , Inibidores de Captação de Serotonina , Paroxetina , Sertralina , PubMed , Fungos
5.
PLoS One ; 17(12): e0271217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36480503

RESUMO

Depression in mammals is known to be associated with poor reproductive capacity. In males, it has been associated with decreased efficiency of spermatogenesis as well as the production of spermatozoa of reduced structural and functional integrity. Although antidepressants are effective in correcting depressive states, there is controversy regarding their effectiveness in restoring male reproductive function. Here, using an animal model of depression induced by a forced swim test, we confirmed that depression is accompanied by impaired male reproductive function. We further show that administration of a conventional antidepressant of the serotonin reuptake inhibitor class (paroxetine) impairs male reproductive performance in terms of sperm production and quality when administered to healthy animals. Intriguingly, when paroxetine is administered to "depressed" animals, it resulted in a complete restoration of the animal's ability to produce sperm that appears to be as capable of meeting the parameters evaluated here as those of control animals. The one-carbon cycle (1CC) is one of the most important metabolic cycles that include the methionine and folate cycles and plays a major role in DNA synthesis, amino acids, and also the production of antioxidants. Our results show that depression affects the main components of this cycle and paroxetine on healthy mice increases homocysteine levels, decreases glycine and vitamin B12, while in depressed mice, it increases folate levels and decreases vitamin B12. Thus, paroxetine exerts negative impacts on male reproductive function when administered to healthy animals and it well correlate with the altered sperm parameters and functions of depressed animals, and its mechanism remains to be explored.


Assuntos
Paroxetina , Sêmen , Masculino , Camundongos , Animais , Paroxetina/farmacologia , Paroxetina/uso terapêutico , Modelos Animais , Espermatozoides , Vitamina B 12 , Ácido Fólico , Mamíferos
6.
J Med Case Rep ; 16(1): 431, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36403006

RESUMO

BACKGROUND: Obsessive-compulsive disorder is a condition in which patients experience an obsession and/or a compulsion. It has a high impact on the quality of life, and is associated with an increased prevalence of psychiatric comorbidities in patients. Onychotillomania is an underestimated psychodermatosis caused by repeated self-inflicted damage to the nail unit. In patients, it is characterized by an obsessive or irrepressible impulse to repeatedly damage their own nails, resulting in their destruction. It is a chronic condition that is difficult to manage, largely because of its psychocutaneous character, as well as its high tendency to interact with underlying neuropsychiatric diseases or other behavioral disorders. Only a few studies have reported an association between obsessive-compulsive disorder and onychotillomania, which typically presents with therapeutic challenges. Cognitive behavioral therapy, physical-barrier approaches, and pharmaceutical treatments have been reported to be beneficial in the management of onychotillomania; however, no major clinical studies have investigated the effectiveness of these therapies. Onychotillomania remains a clinical and therapeutic issue owing to the lack of evidence-based treatment techniques. CASE PRESENTATION: We report a case of an 18-year-old, middle-eastern female patient who developed onychotillomania when she was being treated with paroxetine for obsessive-compulsive disorder and was showing partial improvement. The patient developed side effects from paroxetine, and was switched to fluoxetine. Thereafter, improvement in her obsessive-compulsive disorder was observed, which relapsed when treatment was discontinued. However, the onychotillomania symptoms did not reemerge. CONCLUSION: Onychotillomania typically presents both diagnostic and therapeutic challenges. Fluoxetine plays an important role in the treatment of onychotillomania and other psychiatric disorders. However, large-scale studies should be conducted before these outcomes can be generalized.


Assuntos
Fluoxetina , Transtorno Obsessivo-Compulsivo , Humanos , Feminino , Adolescente , Fluoxetina/uso terapêutico , Paroxetina/uso terapêutico , Qualidade de Vida , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Preparações Farmacêuticas
7.
Zhongguo Zhen Jiu ; 42(11): 1211-5, 2022 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-36397216

RESUMO

OBJECTIVE: To observe the effect of Huayu Tongluo (resolving stasis and promoting collateral circulation) moxibustion combined with intradermal needling on depressive symptoms, quality of life and cognitive impairment in patients with mild to moderate depression after cerebral infarction on the basis of western medicine treatment. METHODS: Fifty patients with mild to moderate depression after cerebral infarction were randomly divided into an acupuncture combined with western medication group (group A, 25 cases) and a western medication group (group B, 25 cases). In the group B, paroxetine hydrochloride tablets were taken orally, 20 mg after breakfast, once a day, and the dose could be adjusted to the maximum 40 mg/d according to the patients' condition, for 4 weeks totally. On the basis of the treatment in the group B, the group A was treated with Huayu Tongluo moxibustion, namely aconite cake-separated moxibustion at Baihui (GV 20) and suspended moxibustion at Dazhui (GV 14) and Shenting (GV 24), combined with intradermal needling at Shenmen (HT 7), Jianshi (PC 5), Zusanli (ST 36), etc. Huayu Tongluo moxibustion was performed 6 times a week, and intradermal needling was performed 3 times a week,for 4 weeks totally. In the two groups, the scores of Hamilton depression scale (HAMD), stroke specific quality of life scale (SS-QOL) and mini mental state examination (MMSE) were observed before and after treatment, and the clinical efficacy and safety were compared. RESULTS: After treatment, the HAMD score in the each group was decreased compared with that before treatment (P<0.05), and that in the group A was lower than the group B (P<0.05); after treatment, the SS-QOL score in the group A and MMSE score in the two groups were increased compared with those before treatment (P<0.05), and the SS-QOL score in the group A was higher than the group B (P<0.05). The total effective rate was 88.0% (22/25) in the group A, which was higher than 60.0% (15/25) in the group B (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (4.0% [1/25] vs 16.0%[4/25], P>0.05). CONCLUSION: On the basis of the treatment of western medication paroxetine hydrochloride tablets, Huayu Tongluo moxibustion combined with intradermal needling therapy can effectively improve the depressive symptoms, quality of life and cognitive impairment of patients with mild to moderate depression after cerebral infarction.


Assuntos
Moxibustão , Humanos , Qualidade de Vida , Paroxetina , Depressão/etiologia , Depressão/terapia , Infarto Cerebral/complicações , Infarto Cerebral/terapia
8.
Am J Case Rep ; 23: e938268, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36366736

RESUMO

BACKGROUND Serotonin toxicity, often referred to as 'serotonin syndrome,' is a drug-induced condition due to excess serotonin released from brain synapses, resulting in symptoms that may be autonomic, neuromuscular, and/or cognitive in nature. Most cases involve more than 1 of the following drug regimens: monoamine oxidase inhibitors (MAOIs), serotonin releasers, selective serotonin reuptake inhibitors (SSRIs), or serotonin-norepinephrine reuptake inhibitors (SNRIs). This report is of a 70-year-old woman who presented with confusion and muscle spasms due to serotonin toxicity associated with paroxetine and quetiapine treatment. CASE REPORT An elderly woman with dementia presented to the Emergency Department with fever, altered mental status, labile blood pressures, and inducible clonus. No known medication dosage increases had been made, nor had any new serotonergic agents been added to the patient's drug regimen. She underwent a thorough workup in the Emergency Department and later during her hospitalization. A presumptive diagnosis of serotonin toxicity was made early on during her stay, with the etiology attributed to use of paroxetine and quetiapine. Clinical improvement was observed after benzodiazepine administration, discontinuation of offending agents, and a brief cyproheptadine course. The patient survived her hospital stay and was ultimately discharged to hospice care with a return to her baseline level of functioning. CONCLUSIONS Diagnosing serotonin toxicity requires a high degree of clinical suspicion and can occur in the absence of increased dosage of existing, or initiation of new, serotonergic agents.


Assuntos
Paroxetina , Síndrome da Serotonina , Feminino , Humanos , Idoso , Paroxetina/efeitos adversos , Síndrome da Serotonina/induzido quimicamente , Síndrome da Serotonina/diagnóstico , Fumarato de Quetiapina/efeitos adversos , Serotonina , Espasmo/tratamento farmacológico
9.
Life Sci ; 311(Pt A): 121143, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36328074

RESUMO

AIMS: P2X receptors are ATP-gated ion channels which play a role in many pathophysiological conditions. They are considered as novel drug targets, particularly in the fields of pain, (neuro) inflammation, and cancer. Due to difficulties in developing drug-like orthosteric ligands that bind to the highly polar ATP binding site, the design of positive and negative allosteric modulators (PAMs and NAMs) is a promising strategy. The P2X4 receptor was proposed as a novel target for neuropathic and inflammatory pain (antagonists), and for the treatment of alcoholism (PAMs). So far, little is known about the allosteric binding site(s) of P2X4 receptors. The aim of this study was to identify the binding site(s) of the macrocyclic natural product ivermectin, the urea derivative BX430, and the antidepressant drug paroxetine that act as allosteric modulators of P2X4 receptors. MATERIAL AND METHODS: We generated chimeric receptors in which extracellular sequences of the human P2X4 receptor were exchanged for corresponding residues of the human P2X2 receptor, complemented by specific single amino acid residue mutants. Chimeric and mutated receptors were stably expressed in 1321N1 astrocytoma cells, and characterized by fluorimetric measurement of ATP-induced Ca2+-influx. In addition, docking studies utilizing a homology model of the human P2X4 receptor were performed. KEY FINDINGS: Our results suggest a common binding site for ivermectin and BX430 in an extracellular receptor domain, while paroxetine might bind to the cation pore. SIGNIFICANCE: The obtained results provide a basis for the development of positive and negative allosteric P2X4 modulators with improved properties and will support future drug development efforts.


Assuntos
Paroxetina , Receptores Purinérgicos P2X4 , Humanos , Receptores Purinérgicos P2X4/metabolismo , Ivermectina , Sítios de Ligação , Dor , Trifosfato de Adenosina/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-36361481

RESUMO

Paroxetine is a common pharmaceutical to treat depression and has been found to pose threats to aquatic organisms. However, little is known about the effects of paroxetine on the nutrient cycle in aquatic environments. Therefore, DNA metabarcoding is used in this study to analyze the effects of paroxetine on multi-trophic microorganisms and nitrogen transformation in river sediments. Although paroxetine has no significant effect on the diversity of microbenthos, changes in benthic nitrogen-converting bacteria are consistent with the change in the various forms of nitrogen in the sediment, indicating that paroxetine affects the nitrogen conversion process by affecting nitrogen-converting bacteria. In addition, it is found that paroxetine has the ability to influence nitrogen transformation in an indirect way by affecting the trophic transfer efficiency of higher trophic levels (meiofauna and protozoa, protozoa and protozoa), subsequently affecting the growth of nitrogen-converting bacteria through a top-down mechanism (i.e., predation).The results show that paroxetine affects nitrogen transformation directly by affecting nitrogen-converting bacteria and indirectly through top-down effects, emphasizing that the assessment of paroxetine's ecological risks should consider species within different trophic levels.


Assuntos
Cadeia Alimentar , Rios , Nitrogênio , Paroxetina/farmacologia , Organismos Aquáticos , Bactérias , Sedimentos Geológicos/microbiologia , Ecossistema
11.
Front Immunol ; 13: 1032497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275707

RESUMO

G protein-coupled receptor (GPCR) kinase 2 (GRK2), which phosphorylates agonist-occupied GPCRs to promote their desensitization, has been investigated as an attractive therapeutic target for cardiovascular and metabolic diseases. Several GRK2-targeted inhibition strategies have been reported including the use of direct pharmacological inhibitors such as paroxetine (a widely prescribed antidepressant) and its analogs such as compound CCG258747. Cross-linking of high affinity IgE receptor (FcϵRI) on mast cells (MCs) and the resulting degranulation causes anaphylaxis and allergic asthma. Using gene silencing strategy, we recently showed that GRK2 contributes to FcεRI signaling and MC degranulation. The purpose of this study was to determine if the GRK2 inhibitors paroxetine and CCG258747 modulate FcεRI-mediated MC responses in vitro and in vivo. Utilizing rat basophilic leukemia (RBL-2H3) cells and primary mouse lung MCs (LMCs), we found that paroxetine and CCG258747 inhibit FcϵRI-mediated calcium mobilization and degranulation. Furthermore, intravenous administration of paroxetine and CCG258747 in mice resulted in substantial reduction of IgE-mediated passive cutaneous anaphylaxis. Unlike LMCs, human cutaneous MCs abundantly express a novel GPCR known as MRGPRX2 (mouse; MRGPRB2). We found that in contrast to their inhibitory effects on FcεRI-mediated MC responses, both paroxetine and CCG258747 induce calcium mobilization and degranulation in RBL-2H3 cells stably expressing MRGPRX2 but not in untransfected cells. Furthermore, paroxetine and CCG258747 induced degranulation in peritoneal MCs from Wild-type (WT) mice in vitro and caused increased cutaneous vascular permeability in vivo, but these responses were substantially reduced in Mrgprb2-/- mice. Additionally, upon intradermal injection, paroxetine also induced neutrophil recruitment in WT but not Mrgprb2-/- mice. These findings suggest that in addition to their potential therapeutic utility against cardiovascular and metabolic disorders, paroxetine-based GRK2-inhibitors may serve to modulate IgE-mediated anaphylaxis and to enhance cutaneous host defense by harnessing MC's immunomodulatory property through the activation of MRGPRX2/MRGPRB2.


Assuntos
Anafilaxia , Mastócitos , Ratos , Camundongos , Humanos , Animais , Mastócitos/metabolismo , Anafilaxia/tratamento farmacológico , Anafilaxia/metabolismo , Paroxetina/farmacologia , Paroxetina/metabolismo , Receptores de IgE/metabolismo , Cálcio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Imunoglobulina E/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de Neuropeptídeos/metabolismo
13.
JAMA ; 328(14): 1405-1414, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36219407

RESUMO

Importance: Opioids can cause severe respiratory depression by suppressing feedback mechanisms that increase ventilation in response to hypercapnia. Following the addition of boxed warnings to benzodiazepine and opioid products about increased respiratory depression risk with simultaneous use, the US Food and Drug Administration evaluated whether other drugs that might be used in place of benzodiazepines may cause similar effects. Objective: To study whether combining paroxetine or quetiapine with oxycodone, compared with oxycodone alone, decreases the ventilatory response to hypercapnia. Design, Setting, and Participants: Randomized, double-blind, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) with 25 healthy participants from January 2021 through May 25, 2021. Interventions: Oxycodone 10 mg on days 1 and 5 and the following in a randomized order for 5 days: paroxetine 40 mg daily, quetiapine twice daily (increasing daily doses from 100 mg to 400 mg), or placebo. Main Outcomes and Measures: Ventilation at end-tidal carbon dioxide of 55 mm Hg (hypercapnic ventilation) using rebreathing methodology assessed for paroxetine or quetiapine with oxycodone, compared with placebo and oxycodone, on days 1 and 5 (primary) and for paroxetine or quetiapine alone compared with placebo on day 4 (secondary). Results: Among 25 participants (median age, 35 years [IQR, 30-40 years]; 11 female [44%]), 19 (76%) completed the trial. The mean hypercapnic ventilation was significantly decreased with paroxetine plus oxycodone vs placebo plus oxycodone on day 1 (29.2 vs 34.1 L/min; mean difference [MD], -4.9 L/min [1-sided 97.5% CI, -∞ to -0.6]; P = .01) and day 5 (25.1 vs 35.3 L/min; MD, -10.2 L/min [1-sided 97.5% CI, -∞ to -6.3]; P < .001) but was not significantly decreased with quetiapine plus oxycodone vs placebo plus oxycodone on day 1 (33.0 vs 34.1 L/min; MD, -1.2 L/min [1-sided 97.5% CI, -∞ to 2.8]; P = .28) or on day 5 (34.7 vs 35.3 L/min; MD, -0.6 L/min [1-sided 97.5% CI, -∞ to 3.2]; P = .37). As a secondary outcome, mean hypercapnic ventilation was significantly decreased on day 4 with paroxetine alone vs placebo (32.4 vs 41.7 L/min; MD, -9.3 L/min [1-sided 97.5% CI, -∞ to -3.9]; P < .001), but not with quetiapine alone vs placebo (42.8 vs 41.7 L/min; MD, 1.1 L/min [1-sided 97.5% CI, -∞ to 6.4]; P = .67). No drug-related serious adverse events were reported. Conclusions and Relevance: In this preliminary study involving healthy participants, paroxetine combined with oxycodone, compared with oxycodone alone, significantly decreased the ventilatory response to hypercapnia on days 1 and 5, whereas quetiapine combined with oxycodone did not cause such an effect. Additional investigation is needed to characterize the effects after longer-term treatment and to determine the clinical relevance of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT04310579.


Assuntos
Analgésicos Opioides , Antidepressivos , Oxicodona , Paroxetina , Fumarato de Quetiapina , Insuficiência Respiratória , Adulto , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacologia , Antidepressivos/efeitos adversos , Antidepressivos/farmacologia , Benzodiazepinas/efeitos adversos , Benzodiazepinas/farmacologia , Dióxido de Carbono/análise , Método Duplo-Cego , Feminino , Humanos , Hipercapnia/etiologia , Oxicodona/efeitos adversos , Oxicodona/farmacologia , Paroxetina/efeitos adversos , Paroxetina/farmacologia , Fumarato de Quetiapina/efeitos adversos , Fumarato de Quetiapina/farmacologia , Respiração/efeitos dos fármacos , Insuficiência Respiratória/induzido quimicamente , Insuficiência Respiratória/diagnóstico
14.
PLoS One ; 17(10): e0267423, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36201406

RESUMO

INTRODUCTION: Clinical Depression and the subsequent low immunity is a comorbidity that can act as a risk factor for the severity of COVID-19 cases. Antidepressants such as Selective serotonin reuptake inhibitor and Serotonin-norepinephrine reuptake inhibitors are associated with immune-modulatory effects, which dismiss inflammatory responses and reduce lung tissue damage. The current systematic review and meta-analysis aims to evaluate the effect of antidepressant drugs on the prognosis and severity of COVID-19 in hospitalized patients. METHODS: A systematic search was carried out in PubMed/Medline, EMBASE, and Scopus up to June 14, 2022. The following keywords were used: "COVID-19", "SARS-CoV-2", "2019-nCoV", "SSRI", "SNRI", "TCA", "MAOI", and "Antidepressant". A fixed or random-effect model assessed the pooled risk ratio (RR) with 95% CI. We considered P < 0.05 as statistically significant for publication bias. Data were analyzed by Comprehensive Meta-Analysis software, Version 2.0 (Biostat, Englewood, NJ). RESULTS: Fourteen studies were included in our systematic review. Five of them were experimental with 2350, and nine of them were observational with 290,950 participants. Eight out of fourteen articles revealed the effect of antidepressants on reducing the severity of COVID-19. Selective serotonin reuptake inhibitors drugs, including Fluvoxamine, Escitalopram, Fluoxetine, and Paroxetine, and among the Serotonin-norepinephrine inhibitors medications Venlafaxine, are reasonably associated with reduced risk of intubation or death. Five studies showed no significant effect, and only one high risk of bias article showed the negative effect of antidepressants on the prognosis of Covid-19. The meta-analysis of clinical trials showed that fluvoxamine could significantly decrease the severity outcomes of COVID-19 (RR: 0.763; 95% CI: 0.602-0.966, I2: 0.0). FINDINGS: Most evidence supports that the use of antidepressant medications, mainly Fluvoxamine, may decrease the severity and improve the outcome in hospitalized patients with SARS-CoV-2. Some studies showed contradictory findings regarding the effects of antidepressants on the severity of COVID-19. Further clinical trials should be conducted to clarify the effects of antidepressants on the severity of COVID-19.


Assuntos
Antidepressivos/uso terapêutico , Fluoxetina/uso terapêutico , Fluvoxamina/uso terapêutico , Humanos , Norepinefrina , Paroxetina/uso terapêutico , SARS-CoV-2 , Serotonina , Cloridrato de Venlafaxina
15.
Drug Des Devel Ther ; 16: 3297-3314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193286

RESUMO

Objective: The mechanism of Wendan Decoction (WDD) against Generalized Anxiety Disorder (GAD) was predicted by network pharmacology and validated by in vivo and in vitro experiments. Methods: The targets of WDD for the treatment of GAD were obtained by a search of online databases. Further, PPI network and KEGG enrichment were used to identify the key targets and pathways. Ultimately, these key targets and pathways were validated by in vivo experiments on GAD mice modeled by repeated restraint stress (RRS) and in vitro experiments on inflammatory factor stimulated BV-2 cells. Results: Through searching the databases, the 137 ingredients of WDD that correspond to 938 targets and 4794 targets related to GAD were identified. Among them, 569 overlapping targets were considered as the therapeutic targets of WDD for GAD. PPI analysis showed that the inflammation-related proteins IL-6, TNF, SRC and AKT1 were the key targets, and KEGG enrichment suggested that PI3K/AKT and MAPK signaling pathways were key pathways of WDD in the treatment of GAD. In vivo experiments, RRS mice exhibited abnormality in behavioristics in open field test (OFT) and elevated plus maze (EPM) and increases in serum corticosterone and the percentage of lymphocytes positive for IL-6 in peripheral blood. These abnormal changes can be reversed by WDD and the positive control drug paroxetine. In vitro experiments, WDD can inhibit IL-6 induced activation of PI3K/AKT and MAPK signaling pathways in BV2 cells, and suppress the ensuing release of inflammatory factors TNF-α, IL-1ß and PGE2, and showed a dose-dependent effect. Conclusion: WDD is able to resist GAD by relieving inflammatory response in peripheral and central system.


Assuntos
Medicamentos de Ervas Chinesas , Fosfatidilinositol 3-Quinases , Animais , Transtornos de Ansiedade/tratamento farmacológico , Corticosterona , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Interleucina-6 , Camundongos , Simulação de Acoplamento Molecular , Paroxetina , Prostaglandinas E , Proteínas Proto-Oncogênicas c-akt , Fator de Necrose Tumoral alfa
16.
Hum Psychopharmacol ; 37(6): e2855, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36194639

RESUMO

OBJECTIVES: Immune dysregulation plays a key role in major depressive disorder (MDD). However, little is known about the complicated involvement of various interleukins in MDD. This study was performed to investigate the correlation between plasma interleukin-8 (IL-8) levels and treatment outcome of paroxetine (a selective serotonin reuptake inhibitor) in patients with MDD. METHODS: A total of 115 hospitalized patients (36 males and 79 females), aged from 18 to 72 years, were enrolled. Plasma levels of IL-8 were measured before treatment initiation (baseline) and at 8 weeks after oral paroxetine treatment. Efficacy of paroxetine was evaluated by use of the Hamilton Depression Rating Scale (HAMD-17). Baseline IL-8 levels were compared between responders and non-responders to paroxetine treatment. RESULTS: Plasma IL-8 levels decreased significantly after an 8-week antidepressant treatment in responders, in association with a dramatic decrease in HAMD-17 scores. In non-responders, plasma IL-8 levels did not change significantly at 8 weeks after antidepressant treatment. Baseline plasma IL-8 levels were found to be significantly lower in responders than in non-responders, showing a correlation between IL-8 and antidepressant response to paroxetine. CONCLUSIONS: These results indicate that plasma IL-8 levels were related to treatment outcome of paroxetine, and therefore suggest that IL-8 could be a promising predicator of treatment response in individual patients with MDD.


Assuntos
Transtorno Depressivo Maior , Paroxetina , Masculino , Feminino , Humanos , Paroxetina/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Interleucina-8 , /uso terapêutico , Antidepressivos/uso terapêutico , Resultado do Tratamento
17.
Neuroreport ; 33(15): 669-680, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36126265

RESUMO

Adverse psychological states are stimulated by multiple types of environmental factors in human being. However, only few animal models of adverse psychological states were established by applying multiple types of stressors to mimic real conditions. A multisensory stress simulation device was designed to apply a combination of stressors to animals. Selected types and intensity of stressors were stimulated by this multisensory stress simulation device to induce chronic multiple mild stress (CMMS) in rats, modeling sustained adverse psychological states caused by long-term exposure in relative extreme environments with limited social interaction in human being. Fourteen-day treatment of CMMS-induced anhedonia, anxiety, and the loss of body weight in rats, which were similar to those in human being with adverse psychological states. Moreover, CMMS treatment leads to decreased production of serotonin and increased expression of corticotropin-releasing factor receptor 1, adrenocorticotropic hormone, and glucocorticoid in the brain, which were prevented by paroxetine and sertraline, two clinical-used antidepressants. Furthermore, these antidepressants prevented the CMMS-induced inhibition of brain-derived neurotrophic factor/cAMP-response element binding protein pathway, reduction of synaptic protein expression, and the activation of microglia and astrocytes in the hippocampus and the prefrontal cortex of rats. In addition, 14-day CMMS-induced long-term depressive-like behaviors, even after 14 days of CMMS treatment. And sertraline reversed CMMS-induced behavioral and biochemical changes in rats. All these results suggested that CMMS protocol induced sustained adverse psychological states in rats. By adjusting the intensity and the type of stressors in the multisensory stress simulation device, it might be practicable to establish animal models with complicated and changeable environmental factors.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Estresse Psicológico , Hormônio Adrenocorticotrópico , Animais , Glucocorticoides , Humanos , Paroxetina , Ratos , Serotonina , Sertralina , Estresse Psicológico/metabolismo
18.
J Affect Disord ; 318: 231-237, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36084758

RESUMO

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been associated with type 2 diabetes mellitus (T2DM) in youths, possibly via 5-HT2C, H1 receptors and serotonin transporter (SERT). SSRIs have similar affinity for SERT but variable affinity for 5-HT2C and H1. This study assessed whether SSRIs with strong affinity for 5-HT2C and H1 (relative to SERT) were associated with T2DM risk compared with weak-affinity SSRIs. METHODS: Using the UK Clinical Practice Research Datalink, we assembled a cohort of patients aged 5-24, newly prescribed a strong-affinity SSRI (citalopram, escitalopram, fluoxetine) or weak affinity (paroxetine, sertraline, fluvoxamine) between 1990 and 2019. We controlled for confounding using standardized mortality ratio weighting, estimated from calendar time-specific propensity scores. We used weighted Cox proportional hazards models to estimate hazard ratios (HRs) of incident T2DM with 95 % confidence intervals (CIs). RESULTS: The cohort included 347,368 new users of strong-affinity SSRIs and 131,359 of weak-affinity SSRIs. Strong-affinity SSRIs were not associated with an increased T2DM risk compared with weak-affinity SSRIs (incidence rate 2.8 vs 2.7 per 1000 person-years; HR 1.03, 95 % CI 0.85-1.25). T2DM risk did not vary with duration of use, age or sex. However, the HR was numerically higher in youths with normal or low weight (HR 1.30, 95 % CI 0.85-1.98) and with prior antipsychotic use (HR 1.62, 95 % CI 0.83-3.18). LIMITATIONS: Median duration of SSRI use, in line with real-world SSRI prescribing, was relatively short. CONCLUSION: T2DM risk did not differ between strong- and weak-affinity SSRIs, providing reassurance for clinicians when choosing between SSRIs in youths.


Assuntos
Antipsicóticos , Diabetes Mellitus Tipo 2 , Adolescente , Citalopram , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Fluoxetina , Fluvoxamina , Humanos , Paroxetina , Serotonina , Proteínas da Membrana Plasmática de Transporte de Serotonina , Sertralina
19.
J Pineal Res ; 73(4): e12832, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36073608

RESUMO

Circadian rhythm disorder is a significant risk factor for mental diseases, and the recovery of circadian rhythm function has gradually become a signal of effective antidepressant therapy. Sini powder (SNP) is a classical, traditional Chinese formula for depression treatment. However, few clinical reports have been recorded. This randomized, double-blinded, controlled trial (ChiCTR1900022700) aimed to explore the efficacy of SNP on depression via regulating circadian rhythm. In total, 36 patients with major depressive disorder (MDD) were enrolled for 4-weeks medication and 6-weeks follow-up. HAMD-24 score and circadian rhythm index, including dim light melatonin onset (DLMO) and phase angle difference (PAD), were included in the assessment. DLMO and PAD were statistically significant in the SNP group after 4 weeks of treatment (p < .05) and with greater improvement in DLMO (p = .03). In addition, DLMO and the HAMD-24 score showed a positive correlation (p < .05); the HAMD-24 score degree decreased significantly over time (p < .001). Similarly, interaction effects were shown significantly between group and time (p = .049). The duration of SNP supplementation was relatively short, and the sample size was relatively small. SNP granules combined with paroxetine tablets have definite efficacy in improving the circadian rhythms of MDD patients, reflecting the therapeutic advantages of traditional Chinese medicine as antidepressants.


Assuntos
Transtorno Depressivo Maior , Medicamentos de Ervas Chinesas , Melatonina , Humanos , Antidepressivos/uso terapêutico , Ritmo Circadiano/fisiologia , Transtorno Depressivo Maior/tratamento farmacológico , Melatonina/metabolismo , Paroxetina/uso terapêutico , Pós/uso terapêutico , Sono/fisiologia , Comprimidos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico
20.
Acta Crystallogr D Struct Biol ; 78(Pt 9): 1099-1109, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048150

RESUMO

Human myeloperoxidase (MPO) utilizes hydrogen peroxide to oxidize organic compounds and as such plays an essential role in cell-component synthesis, in metabolic and elimination pathways, and in the front-line defence against pathogens. Moreover, MPO is increasingly being reported to play a role in inflammation. The enzymatic activity of MPO has also been shown to depend on its glycosylation. Mammalian MPO crystal structures deposited in the Protein Data Bank (PDB) present only a partial identification of their glycosylation. Here, a newly obtained crystal structure of MPO containing four disulfide-linked dimers and showing an elaborate collection of glycans is reported. These are compared with the glycans identified in proteomics studies and from 18 human MPO structures available in the PDB. The crystal structure also contains bound paroxetine, a blocker of serotonin reuptake that has previously been identified as an irreversible inhibitor of MPO, in the presence of thiocyanate, a physiological substrate of MPO.


Assuntos
Paroxetina , Peroxidase , Antidepressivos , Glicosilação , Humanos , Peroxidase/química , Peroxidase/metabolismo , Polissacarídeos/química
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