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1.
Chonnam Medical Journal ; : 20-26, 2020.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-787278

RESUMO

We examined the effect of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on neuronal viability in mouse cortical near-pure neuronal cultures. Addition of fluoxetine to the media for 24 hours induced neuronal death in a concentration-dependent manner. To delineate the mechanisms of fluoxetine-induced neuronal death, we investigated the effects of trolox, cycloheximide (CHX), BDNF, z-VAD-FMK, and various metal-chelators on fluoxetine-induced neuronal death. Neuronal death was assessed by MTT assay. The addition of 20 µM fluoxetine to the media for 24 hours induced 60–70% neuronal death, which was associated with the hallmarks of apoptosis, chromatin condensation and DNA laddering. Fluoxetine-induced death was significantly attenuated by CHX, BDNF, or z-VAD-FMK. Treatment with antioxidants, trolox and ascorbate, also markedly attenuated fluoxetine-induced death. Interestingly, some divalent cation chelators (EGTA, Ca-EDTA, and Zn-EDTA) also markedly attenuated the neurotoxicity. Fluoxetine-induced reactive oxygen species (ROS) generation was measured using the fluorescent dye 2′,7′-dichlorofluorescin diacetate. Trolox and bathocuproine disulfonic acid (BCPS), a cell membrane impermeable copper ion chelator, markedly attenuated the ROS production and neuronal death. However, deferoxamine, an iron chelator, did not affect ROS generation or neurotoxicity. We examined the changes in intracellular copper concentration using a copper-selective fluorescent dye, Phen Green FL, which is quenched by free copper ions. Fluoxetine quenched the fluorescence in neuronal cells, and the quenching effect of fluoxetine was reversed by co-treatment with BCPS, however, not by deferoxamine. These findings demonstrate that fluoxetine could induce apoptotic and oxidative neuronal death associated with an influx of copper ions.


Assuntos
Animais , Antioxidantes , Apoptose , Fator Neurotrófico Derivado do Encéfalo , Morte Celular , Membrana Celular , Quelantes , Cromatina , Cobre , Cicloeximida , Desferroxamina , DNA , Fluorescência , Fluoxetina , Íons , Ferro , Camundongos , Neurônios , Espécies Reativas de Oxigênio , Serotonina
2.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-739534

RESUMO

5-HT₆ receptor (5-HT₆R) is implicated in cognitive dysfunction, mood disorder, psychosis, and eating disorders. However, despite its significant role in regulating the brain functions, regulation of 5-HT₆R at the molecular level is poorly understood. Here, using yeast two-hybrid assay, we found that human 5-HT₆R directly binds to neuro-oncological ventral antigen 1 (Nova-1), a brain-enriched splicing regulator. The interaction between 5-HT₆R and Nova-1 was confirmed using GST pull-down and co-immunoprecipitation assays in cell lines and rat brain. The splicing activity of Nova-1 was decreased upon overexpression of 5-HT₆R, which was examined by detecting the spliced intermediates of gonadotropin-releasing hormone (GnRH), a known pre-mRNA target of Nova-1, using RT-PCR. In addition, overexpression of 5-HT₆R induced the translocation of Nova-1 from the nucleus to cytoplasm, resulting in the reduced splicing activity of Nova-1. In contrast, overexpression of Nova-1 reduced the activity and the total protein levels of 5-HT₆R. Taken together, these results indicate that when the expression levels of 5-HT₆R or Nova-1 protein are not properly regulated, it may also deteriorate the function of the other.


Assuntos
Animais , Encéfalo , Linhagem Celular , Citoplasma , Ingestão de Alimentos , Hormônio Liberador de Gonadotropina , Humanos , Imunoprecipitação , Transtornos do Humor , Transtornos Psicóticos , Ratos , Precursores de RNA , Proteínas de Ligação a RNA , Serotonina , Técnicas do Sistema de Duplo-Híbrido
3.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-787404

RESUMO

OBJECTIVES: The purpose of this study was to compare aripiprazole versus bupropion augmentation therapy in older adult patients with major depressive disorder unresponsive to selective serotonin reuptake inhibitors(SSRIs).METHODS: This is a post-hoc analysis of a 6-week, randomized prospective open-label multi-center study in thirty older adult patients with major depressive disorder. Participants were randomized to receive aripiprazole(N=16, 2.5–10mg/day) or bupropion(N=14, 150–300mg/day) for 6 weeks. Montgomery Asberg Depression Rating Scale (MADRS), 17-item Hamilton Depression Rating scale(HAM-D17), Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores, and Clinical Global Impression-Severity (CGI-S) were obtained at baseline and after one, two, four, and six weeks. Changes on individual items of HAM-D17 were assessed as well as on composite scales(anxiety, insomnia and drive), and on four core subscales that capture core depression symptoms.RESULTS: There was a significantly greater decrease in MADRS scores in aripiprazole group compared to bupropion group at 4(p<0.05) and 6(p<0.05) weeks. There were significantly higher response rate at week 4(p<0.05) and 6(p<0.05) and remission rate at week 6 in aripiprazole group compared to bupropion group. Individual HAM-D17 items showing significantly greater change with adjunctive aripiprazole than bupropion: insomnia, late(ES=0.81 vs. −0.24, p=0.043), psychomotor retardation(ES=1.30 vs. 0.66, p=0.024), general somatic symptoms(ES=1.24 vs. 0.00, p=0.01). On three composite scales, adjunctive aripiprazole was significantly more effective than bupropion with respect to mean change for drive(p=0.005).CONCLUSION: Results of this study suggested that aripiprazole augmentation have superior efficacy in treating general and core symptoms of depression in older adult patients. Aripiprazole augmentation is associated with greater improvement in specific symptoms of depression such as psychomotor retardation, general somatic symptoms and drive.


Assuntos
Adulto , Aripiprazol , Bupropiona , Depressão , Transtorno Depressivo Maior , Fadiga , Humanos , Iowa , Estudos Prospectivos , Serotonina , Distúrbios do Início e da Manutenção do Sono , Pesos e Medidas
4.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-787403

RESUMO

Depression is almost twice as prevalent in women than men. Atypical symptoms, somatic complaints, and comorbid anxiety disorders are more common in women, whereas suicide and comorbid substance use disorders are more common in men. Previous studies have also reported gender differences in the efficacy of and tolerability to specific classes of antidepressants. Various psychosocial and biological factors have been proposed to explain the gender differences in clinical characteristics of depression. The predominant theory of depression pathogenesis is the monoamine hypothesis, and consequently, monoamine neurotransmitters have been the primary target of antidepressants. In the first section of this review, study findings of clinical differences in depression by gender are summarized. Then, we provide an overview of the findings from human and rodent studies of gender differences in serotonin, norepinephrine, dopamine, and glutamate neurotransmitter systems. Total level, rate of synthesis, and receptor profiles of neurotransmitters seem to differ by gender in the euthymic state, depressed state, and in responses to stress or antidepressants. Furthermore, these neurotransmitters interact with gonadal hormones and the hypothalamic-pituitary-adrenal axis, systems that innately exhibit gender differences. Although most of the studies conducted so far are limited to animal models and results of the studies are heterogeneous, growing evidence suggests that gender differences exist in neurotransmitter systems, which possibly leads to gender differences in depression. More intensive studies in this field are needed to build gender-specific treatment strategies.


Assuntos
Antidepressivos , Transtornos de Ansiedade , Fatores Biológicos , Depressão , Dopamina , Feminino , Ácido Glutâmico , Hormônios Gonadais , Humanos , Masculino , Modelos Animais , Neurotransmissores , Norepinefrina , Roedores , Serotonina , Transtornos Relacionados ao Uso de Substâncias , Suicídio
5.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-766566

RESUMO

Suicide is a complex phenomenon resulting from interactions between individual vulnerabilities and socio-environmental factors. The current review primarily focuses on research into the serotonin system, hypothalamic-pituitary-adrenal axis, neurotrophic factors, lipid metabolism, and functional neuroimaging studies. It has been found that dysfunctions in the serotonin system, hypothalamic-pituitary-adrenal axis abnormalities, and low brain-derived neurotrophic factor and cholesterol levels may be linked to suicide. Additionally, recent neuroimaging studies have suggested that structural and functional abnormalities in brain areas related to cognitive and emotional regulation may be associated with suicide. More research incorporating advanced methodological approaches may shed further light on the neurobiological basis of suicide.


Assuntos
Encéfalo , Fator Neurotrófico Derivado do Encéfalo , Colesterol , Neuroimagem Funcional , Metabolismo dos Lipídeos , Fatores de Crescimento Neural , Neurobiologia , Neuroimagem , Sistema Hipófise-Suprarrenal , Serotonina , Suicídio
6.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-765968

RESUMO

BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) often report poor sleep quality. Whether poor sleep is associated with tryptophan (Trp) metabolites is unknown. We compared serum Trp metabolites in women with IBS and healthy controls (HCs) using targeted liquid chromatography mass spectrometry (LC-MS)-based profiling. In IBS only, we explored whether Trp metabolites are associated with IBS symptoms and subjective and objective sleep indices, serum cortisol, plasma adrenocorticotropic hormone (ACTH), and cortisol/ACTH levels. METHODS: Blood samples were obtained every 80 minutes in 21 HCs and 38 IBS subjects following an anticipation-of-public-speaking stressor during a sleep laboratory protocol. Subjects completed symptom diaries for 28 days. Adjacent values of metabolites were averaged to represent 4 time-periods: awake, early sleep, mid-sleep, and mid-to-late sleep. Thirteen of 20 targeted Trp metabolites were identified. RESULTS: Ten of 13 Trp metabolites decreased across the night, while nicotinamide increased in both groups. A MANOVA omnibus test performed after principal component analysis showed a significant difference in these 13 principal component (P = 0.014) between groups. Compared to HCs, nicotinamide levels were higher and indole-3-lactic acid levels lower in the IBS group. Melatonin and indole-3-acetic acid levels were associated with several subjective/objective sleep measures; decreased stool consistency/frequency and abdominal pain were positively associated with melatonin and serotonin in the IBS group. The kynurenine and kynurenic acid were associated with ACTH (positively) and cortisol/ACTH (negatively). CONCLUSIONS: Nighttime Trp metabolites may provide clues to poor sleep and stress with IBS. Further study of the mechanism of metabolite action is warranted.


Assuntos
Dor Abdominal , Hormônio Adrenocorticotrópico , Cromatografia Líquida , Feminino , Humanos , Hidrocortisona , Síndrome do Intestino Irritável , Ácido Cinurênico , Cinurenina , Espectrometria de Massas , Melatonina , Niacinamida , Plasma , Análise de Componente Principal , Serotonina , Triptofano
7.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-765096

RESUMO

BACKGROUND: Although some strategies are used for prophylaxis of contrast induced nephropathy, their efficacy is not fully established. Sarpogrelate can relieve vasospasm and have anti-inflammatory action. This study examined whether sarpogrelate reduces the incidence of contrast induced nephropathy (CIN) or subsequent renal impairment during four weeks after coronary angiography compared with a control group. METHODS: Seventy-four participants with chronic renal failure were randomly assigned to the sarpogrelate or control group. Patients assigned to the sarpogrelate group received oral saporogelate from 24 hours before contrast exposure up to one month after contrast exposure. The primary outcome of this study was the incidence of CIN within 48 hours after exposure to the contrast agent. RESULTS: Thirty-one subjects in the control group and 35 subjects in the sarpogrelate group were used for the analysis. Cumulative CIN occurred numerically more at 48 hours in the sarpogrelate group and less at one month without statistical significance (11.4% vs. 6.5% at 48 hours and 11.4% vs. 16.1% at one month, respectively). Baseline renal function was similar in both groups, but the estimated glomerular filtration rate (eGFR) was lower in the sarpogrelate group at 12 and 48 hours compared with the control group (45.6 vs. 54.7 mL/min/1.73m²; P = 0.023 and 39.9 vs. 50.6 mL/min/1.73m²; P = 0.020, respectively). At one month, the eGFR became comparable between the two groups because the eGFR was aggravated in the control group and maintained in the sarpogrelate group. CONCLUSION: This study failed to demonstrate that sarpogrelate has a renoprotective effect against contrast induced acute kidney injury. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01165567


Assuntos
Lesão Renal Aguda , Angiografia Coronária , Taxa de Filtração Glomerular , Humanos , Incidência , Falência Renal Crônica , Estudos Prospectivos , Insuficiência Renal , Serotonina
8.
Epidemiology and Health ; : e2019026-2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763737

RESUMO

OBJECTIVES: Severe complications of tramadol overdose have been reported; however, few large-scale studies have investigated this issue. Therefore, this study aimed to explore the presentation and complications of tramadol overdose in patients admitted to an intoxication referral center in northwestern Iran. METHODS: Patients with tramadol overdose admitted to Sina Teaching Hospital in Tabriz, Iran during 2013-2017 were included. For each patient, the following data were collected: demographics, previous drug or medication overdose, whether the patient was in the process of quitting drug use, ingested dose of tramadol and co-ingestants, Glasgow Coma Scale (GCS) score, clinical symptoms at the time of admission, and admission characteristics. Serotonin toxicity was diagnosed in patients who fit the Hunter criteria. Multiple logistic regression was performed to identify variables associated with the incidence of severe complications of tramadol overdose. RESULTS: In total, 512 cases of tramadol overdose were evaluated, of which 359 patients were included, with a median age of 41 years (range, 16-69) and a median tramadol dose of 1,500 mg (range, 500-4,000). The most frequent complications associated with tramadol overdose were hypertension (38.4%), tachycardia (24.8%), and seizure (14.5%). No serotonin toxicity was detected in patients. Having a GCS score 1,000 mg, being in the process of quitting drug use, being 30-49 years old, and male sex were significantly related to the incidence of severe complications of tramadol overdose. CONCLUSIONS: Although seizure was prevalent among Iranian patients with tramadol poisoning, serotonin toxicity and cardiogenic shock were rare findings.


Assuntos
Demografia , Escala de Coma de Glasgow , Hospitais de Ensino , Humanos , Hipertensão , Incidência , Irã (Geográfico) , Modelos Logísticos , Masculino , Envenenamento , Encaminhamento e Consulta , Convulsões , Serotonina , Síndrome da Serotonina , Choque Cardiogênico , Taquicardia , Tramadol
9.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763562

RESUMO

Schizophrenic patients resistant to antipsychotics are diagnosed as having treatment-refractory schizophrenia, and they are treated with clozapine. However, clozapine is sometimes combined with electroconvulsive therapy (ECT) if clozapine monotherapy fails. In this report, a severe treatment-refractory schizophrenic patient who did not respond to clozapine even with ECT, but who recovered with asenapine monotherapy, is presented. Asenapine, considered a serotonin spectrum dopamine modulator, is a new atypical antipsychotic with unique pharmacological features that is used not only for schizophrenia, but also for bipolar disorder. The unique features of asenapine may be effective for some treatment-refractory schizophrenic patients.


Assuntos
Antipsicóticos , Transtorno Bipolar , Clozapina , Dopamina , Eletroconvulsoterapia , Humanos , Recidiva , Esquizofrenia , Serotonina , Suicídio
10.
Psychiatry Investigation ; : 948-953, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-786547

RESUMO

OBJECTIVE: Depression is a prevalent condition that is costly to individuals and society. In view of a role of tryptophan (TRP), selenium (Se), vitamin D (Vit D), magnesium (Mg) and serotonin in depression, the present study concerns to evaluate the circulating levels of TRP, Se, Vit D, Mg and serotonin in depression as well as the correlation between TRP and other serum analytes is also established.METHODS: Healthy (n=48) and depressed (n=48) subjects were recruited and their blood samples were obtained after an overnight fast of 12 h, serum was stored for the determination of levels of TRP, Se, Vit D, Mg, and serotonin.RESULTS: show that levels of TRP, Se, Vit D, Mg, and serotonin were decreased in the depressed patient when compared to normal subjects. There is a direct correlation between TRP and Vit D, and TRP and Se while the inverse correlation between TRP and Mg, and TRP and serotonin in depressed subjects. The association among TRP and other biomarkers is non-significant.CONCLUSION: In conclusion, depression is associated with deficiency of TRP, Se, Vit D, Mg, and serotonin displays the characteristics of biomarkers. The correlation between TRP and other biomarkers/trace elements is also important in depression.


Assuntos
Biomarcadores , Depressão , Humanos , Magnésio , Selênio , Serotonina , Oligoelementos , Triptofano , Vitamina D
11.
Epidemiology and Health ; : 2019026-2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-785761

RESUMO

OBJECTIVES: Severe complications of tramadol overdose have been reported; however, few large-scale studies have investigated this issue. Therefore, this study aimed to explore the presentation and complications of tramadol overdose in patients admitted to an intoxication referral center in northwestern Iran.METHODS: Patients with tramadol overdose admitted to Sina Teaching Hospital in Tabriz, Iran during 2013-2017 were included. For each patient, the following data were collected: demographics, previous drug or medication overdose, whether the patient was in the process of quitting drug use, ingested dose of tramadol and co-ingestants, Glasgow Coma Scale (GCS) score, clinical symptoms at the time of admission, and admission characteristics. Serotonin toxicity was diagnosed in patients who fit the Hunter criteria. Multiple logistic regression was performed to identify variables associated with the incidence of severe complications of tramadol overdose.RESULTS: In total, 512 cases of tramadol overdose were evaluated, of which 359 patients were included, with a median age of 41 years (range, 16-69) and a median tramadol dose of 1,500 mg (range, 500-4,000). The most frequent complications associated with tramadol overdose were hypertension (38.4%), tachycardia (24.8%), and seizure (14.5%). No serotonin toxicity was detected in patients. Having a GCS score <15, having taken a tramadol dose of >1,000 mg, being in the process of quitting drug use, being 30-49 years old, and male sex were significantly related to the incidence of severe complications of tramadol overdose.CONCLUSIONS: Although seizure was prevalent among Iranian patients with tramadol poisoning, serotonin toxicity and cardiogenic shock were rare findings.


Assuntos
Demografia , Escala de Coma de Glasgow , Hospitais de Ensino , Humanos , Hipertensão , Incidência , Irã (Geográfico) , Modelos Logísticos , Masculino , Envenenamento , Encaminhamento e Consulta , Convulsões , Serotonina , Síndrome da Serotonina , Choque Cardiogênico , Taquicardia , Tramadol
12.
Asian Spine Journal ; : 1036-1046, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-785481

RESUMO

Antidepressant drugs can be advantageous in treating psychiatric and non-psychiatric illnesses, including spinal disorders. However, spine surgeons remain unfamiliar with the advantages and disadvantages of the use of antidepressant drugs as a part of the medical management of diseases of the spine. Our review article describes a systematic method using the PubMed/Medline database with a specific set of keywords to identify such benefits and drawbacks based on 17 original relevant articles published between January 2000 and February 2018; this provides the community of spine surgeons with available cumulative evidence contained within two tables illustrating both observational (10 studies; three cross-sectional, three case-control, and four cohort studies) and interventional (seven randomized clinical trials) studies. While tricyclic antidepressants (e.g., amitriptyline) and duloxetine can be effective in the treatment of neuropathic pain caused by root compression, venlafaxine may be more appropriate for patients with spinal cord injury presenting with depression and/or nociceptive pain. Despite the potential associated consequences of a prolonged hospital stay, higher cost, and controversial reports regarding the lowering of bone mineral density in the elderly, antidepressants may improve patient satisfaction and quality of life following surgery, and reduce postoperative pain and risk of delirium. The preoperative treatment of preexisting psychiatric diseases, such as anxiety and depression, can improve outcomes for patients with spinal cord injury-related disabilities; however, a preoperative platelet function assay is advocated prior to major spine surgical procedures to protect against significant intraoperative blood loss, as serotonergic antidepressants (e.g., selective serotonin reuptake inhibitors) and bupropion can increase the likelihood of bleeding intraoperatively due to drug-induced platelet dysfunction. This comprehensive review of this evolving topic can assist spine surgeons in better understanding the benefits and risks of antidepressant drugs to optimize outcomes and avoid potential hazards in a spine surgical setting.


Assuntos
Idoso , Antidepressivos , Antidepressivos Tricíclicos , Ansiedade , Plaquetas , Densidade Óssea , Bupropiona , Estudos de Casos e Controles , Estudos de Coortes , Delírio , Depressão , Cloridrato de Duloxetina , Hemorragia , Humanos , Tempo de Internação , Métodos , Neuralgia , Dor Nociceptiva , Dor Pós-Operatória , Satisfação do Paciente , Qualidade de Vida , Medição de Risco , Serotonina , Medula Espinal , Traumatismos da Medula Espinal , Coluna Vertebral , Cirurgiões , Cloridrato de Venlafaxina
13.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-785324

RESUMO

There is considerable overlap in the clinical presentations of apathy and depression. However, differential diagnosis between apathy and other psychiatric conditions, including depression and dementia, is important. In this report, we present the case of a 67-year-old woman with a history of receiving selective serotonin reuptake inhibitor (SSRI) treatment for depression. Differential diagnosis between treatment-resistant depression and SSRI-induced apathy syndrome was required. The symptoms of her apathy syndrome were relieved after the discontinuation of SSRIs and the addition of olanzapine, methylphenidate, and modafinil. Furthermore, we briefly review related literature in this article.


Assuntos
Idoso , Apatia , Demência , Depressão , Diagnóstico Diferencial , Feminino , Humanos , Metilfenidato , Serotonina , Inibidores de Captação de Serotonina
14.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-761812

RESUMO

Escitalopram is one of selective serotonin reuptake inhibitor antidepressants. As an S-enantiomer of citalopram, it shows better therapeutic outcome in depression and anxiety disorder treatment because it has higher selectivity for serotonin reuptake transporter than citalopram. The objective of this study was to determine the direct inhibitory effect of escitalopram on 5-hydroxytryptamine type 3 (5-HT₃) receptor currents and study its blocking mechanism to explore additional pharmacological effects of escitalopram through 5-HT₃ receptors. Using a whole-cell voltage clamp method, we recorded currents of 5-HT₃ receptors when 5-HT was applied alone or co-applied with escitalopram in cultured NCB-20 neuroblastoma cells known to express 5-HT₃ receptors. 5-HT induced currents were inhibited by escitalopram in a concentration-dependent manner. EC50 of 5-HT on 5-HT₃ receptor currents was increased by escitalopram while the maximal peak amplitude was reduced by escitalopram. The inhibitory effect of escitalopram was voltage independent. Escitalopram worked more effectively when it was co-applied with 5-HT than pre-application of escitalopram. Moreover, escitalopram showed fast association and dissociation to the open state of 5-HT₃ receptor channel with accelerating receptor desensitization. Although escitalopram accelerated 5-HT₃ receptor desensitization, it did not change the time course of desensitization recovery. These results suggest that escitalopram can inhibit 5-HT₃ receptor currents in a non-competitive manner with the mechanism of open channel blocking.


Assuntos
Antidepressivos , Transtornos de Ansiedade , Citalopram , Depressão , Métodos , Neuroblastoma , Serotonina
15.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-761794

RESUMO

Mosapride accelerates gastric emptying by acting on 5-hydroxytryptamine type 4 (5-HT₄) receptor and is frequently used in the treatment of gastrointestinal (GI) disorders requiring gastroprokinetic efficacy. We tested the effect of mosapride on 5-hydroxytryptamine type 3 (5-HT₃) receptor currents because the 5-HT₃ receptors are also known to be expressed in the GI system and have an important role in the regulation of GI functions. Using the whole-cell voltage clamp method, we compared the currents of the 5-HT₃ receptors when 5-HT was applied alone or was co-applied with mosapride in cultured NCB-20 cells known to express 5-HT₃ receptors. The 5-HT₃ receptor current amplitudes were inhibited by mosapride in a concentration-dependent manner. Mosapride blocked the peak currents evoked by the application of 5-HT in a competitive manner because the EC₅₀ shifted to the right without changing the maximal effect. The rise slopes of 5-HT₃ receptor currents were decreased by mosapride. Pre-application of mosapride before co-application, augmented the inhibitory effect of mosapride, which suggests a closed channel blocking mechanism. Mosapride also blocked the opened 5-HT₃ receptor because it inhibited the 5-HT₃ receptor current in the middle of the application of 5-HT. It accelerated desensitization of the 5-HT₃ receptor but did not change the recovery process from the receptor desensitization. There were no voltage-, or use-dependency in its blocking effects. These results suggest that mosapride inhibited the 5-HT₃ receptor through a competitive blocking mechanism probably by binding to the receptor in closed state, which could be involved in the pharmacological effects of mosapride to treat GI disorders.


Assuntos
Esvaziamento Gástrico , Métodos , Serotonina
16.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-761789

RESUMO

The lamina II, also called the substantia gelatinosa (SG), of the trigeminal subnucleus caudalis (Vc), is thought to play an essential role in the control of orofacial nociception. Glycine and serotonin (5-hydroxytryptamine, 5-HT) are the important neurotransmitters that have the individual parts on the modulation of nociceptive transmission. However, the electrophysiological effects of 5-HT on the glycine receptors on SG neurons of the Vc have not been well studied yet. For this reason, we applied the whole-cell patch clamp technique to explore the interaction of intracellular signal transduction between 5-HT and the glycine receptors on SG neurons of the Vc in mice. In nine of 13 neurons tested (69.2%), pretreatment with 5-HT potentiated glycine-induced current (I(Gly)). Firstly, we examined with a 5-HT₁ receptor agonist (8-OH-DPAT, 5-HT(1/7) agonist, co-applied with SB-269970, 5-HT₇ antagonist) and antagonist (WAY-100635), but 5-HT₁ receptor agonist did not increase IGly and in the presence of 5-HT₁ antagonist, the potentiation of 5-HT on I(Gly) still happened. However, an agonist (α-methyl-5-HT) and antagonist (ketanserin) of the 5-HT₂ receptor mimicked and inhibited the enhancing effect of 5-HT on I(Gly) in the SG neurons, respectively. We also verified the role of the 5-HT₇ receptor by using a 5-HT₇ antagonist (SB-269970) but it also did not block the enhancement of 5-HT on I(Gly). Our study demonstrated that 5-HT facilitated I(Gly) in the SG neurons of the Vc through the 5-HT₂ receptor. The interaction between 5-HT and glycine appears to have a significant role in modulating the transmission of the nociceptive pathway.


Assuntos
Animais , Glicina , Camundongos , Neurônios , Neurotransmissores , Nociceptividade , Técnicas de Patch-Clamp , Receptores da Glicina , Serotonina , Transdução de Sinais , Substância Gelatinosa
17.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-742212

RESUMO

Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (α), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak D₂ receptor bindings with strong binding to the 5-HT(2A) receptor, while typical antipsychotics block long-lasting, tight D₂ receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.


Assuntos
Sintomas Afetivos , Analgésicos , Antidepressivos , Antipsicóticos , Delusões , Dopamina , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Distonia , Alucinações , Histamina , Humanos , Transtornos dos Movimentos , Norepinefrina , Manejo da Dor , Prolactina , Agitação Psicomotora , Transtornos Psicóticos , Receptor 5-HT2A de Serotonina , Receptores de Neurotransmissores , Serotonina , Ganho de Peso
18.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-741923

RESUMO

To conceptualize a novel bio-psychosocial-behavioral treatment model of panic disorder (PD), it is necessary to completely integrate behavioral, psychophysiological, neurobiological, and genetic data. Molecular genetic research on PD is specifically focused on neurotransmitters, including serotonin, neuropeptides, glucocorticoids, and neurotrophins. Although pharmacological interventions for PD are currently available, the need for more effective, faster-acting, and more tolerable pharmacological interventions is unmet. Thus, glutamatergic receptor modulators, orexin receptor antagonists, corticotrophin-releasing factor 1 receptor antagonists, and other novel mechanism-based anti-panic therapeutics have been proposed. Research on the neural correlates of PD is focused on the dysfunctional “cross-talk” between emotional drive (limbic structure) and cognitive inhibition (prefrontal cortex) and the fear circuit, which includes the amygdala-hippocampus-prefrontal axis. The neural perspective regarding PD supports the idea that cognitive-behavioral therapy normalizes alterations in top-down cognitive processing, including increased threat expectancy and attention to threat. Consistent with the concept of “personalized medicine,” it is speculated that Research Domain Criteria can enlighten further treatments targeting dysfunctions underlying PD more precisely and provide us with better definitions of moderators used to identify subgroups according to different responses to treatment. Structuring of the “negative valence systems” domain, which includes fear/anxiety, is required to define PD. Therefore, targeting glutamate- and orexin-related molecular mechanisms associated with the fear circuit, which includes the amygdala-hippocampus-prefrontal cortex axis, is required to define a novel bio-psychosocial-behavioral treatment model of PD.


Assuntos
Glucocorticoides , Biologia Molecular , Fatores de Crescimento Neural , Neuropeptídeos , Neurotransmissores , Antagonistas dos Receptores de Orexina , Transtorno de Pânico , Pânico , Serotonina
19.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-741921

RESUMO

OBJECTIVE: Classifying mental disorders on the basis of objective makers might clarify their aetiology, help in making the diagnosis, identify “at risk” individuals, determine the severity of mental illness, and predict the course of the disorder. This study aims to review biological and clinical markers of panic disorder (PD). METHODS: A computerized search was carried out in PubMed and Science Direct using the key words: “marker/biomarker/clinical marker/neurobiology/staging” combined using Boolean AND operator with “panic.” In addition, the reference lists from existing reviews and from the articles retrieved were inspected. Only English language papers published in peer-reviewed journals were included. RESULTS: Structural changes in the amygdala, hippocampus, cerebral blood level in the left occipital cortex, serotonin 5-TH and noradrenergic systems activation, aberrant respiratory regulation, hearth rate variability, blood cells and peripheral blood stem cells, hypothalamic–pituitary–adrenal axis dysregulation were identified as potential candidate biomarkers of PD. Staging was identified as clinical marker of PD. According to the staging model, PD is described as follows: prodromal phase (stage 1); acute phase (stage 2); panic attacks (stage 3); chronic phase (stage 4). CONCLUSION: The clinical utility, sensitivity, specificity, and the predictive value of biomarkers for PD is still questionable. The staging model of PD might be a valid susceptibility, diagnostic, prognostic, and predictive marker of PD. A possible longitudinal model of biological and clinical markers of PD is proposed.


Assuntos
Tonsila do Cerebelo , Biomarcadores , Células Sanguíneas , Diagnóstico , Hipocampo , Transtornos Mentais , Lobo Occipital , Transtorno de Pânico , Pânico , Sintomas Prodrômicos , Sensibilidade e Especificidade , Serotonina , Células-Tronco
20.
Biomédica (Bogotá) ; 38(3): 437-450, jul.-set. 2018. graf
Artigo em Espanhol | LILACS (Américas) | ID: biblio-973996

RESUMO

La hipótesis sobre las causas de la depresión basada en la acción de la serotonina y del sistema inmunológico, propone que ciertos tipos de estrés distorsionan la relación entre la actividad del sistema inmunitario innato y la del sistema nervioso central. El estrés causado por una infección o el estrés psicológico excesivo activan receptores de tipo toll, como el TLR-4, el factor de transcripción NF-kB, el inflamasoma NLRP3, así como la secreción de interleucina 1 beta (IL-1ß) e interleucina 6 (IL-6); esto causa, en primer lugar, los síntomas generales de enfermedad que aparecen con cualquier infección, pero también los síntomas característicos de la depresión como disforia y anhedonia. Las evidencias indican que, si el estímulo persiste o se repite en las siguientes 24 horas, se activa la enzima indolamina 2,3-dioxigenasa (IDO) de la vía metabólica de la quinurenina, lo cual incrementa la síntesis del ácido quinolínico y reduce la síntesis de serotonina. El ácido quinolínico activa los receptores de N-metil-D-aspartato (NMDA) en el sistema nervioso central y estimula la secreción de, entre otras, las interleucinas IL-6 e 1L-1ß, las cuales promueven la hiperactividad del eje hipotálamohipófiso-suprarrenal y refuerzan la desviación del metabolismo del triptófano hacia la producción de ácido quinolínico, así como de las interleucinas de la inmunidad innata, con lo cual se reduce más la síntesis de serotonina y se consolida el proceso depresivo. Este proceso puede ser iniciado por las interleucinas estimuladas por una infección, así como por algunas vacunas o por un estrés psicológico excesivo que active el eje hipotálamo-hipófiso-suprarrenal simultáneamente con la respuesta inmunológica innata, con lo que se provocaría un proceso de inflamación estéril en el sistema nervioso central.


The serotonergic and immunological hypothesis of depression proposes that certain types of excessive stress distort the relationship between the activities of the innate immune and central nervous systems, so that the stress caused by an infection, or excessive psychological stress, activate toll-like receptors such as the TLR-4, the transcription factor NF-kB, the inflammasome NLRP3, as well as the secretion of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and other factors of the innate immune response, causing first, the general symptoms of the disease which appear with any infection, but also those characteristic of depressive illness such as dysphoria and anhedonia. The evidence indicates that, if the stimulus persists or recurs within 24 hours, the indole-2, 3-dioxygenase enzyme (IDO) of the kynurenine metabolic pathway, which increases the synthesis of quinolinic acid, is activated with an associated reduction of serotonin synthesis. Quinolinic acid activates NMDA receptors in the central nervous system and stimulates the secretion of interleukins IL-6 and 1L-1ß, among others, promoting hyper-activity of the HPA axis and reinforcing a bias of the tryptophan metabolism to produce quinolinic acid, and interleukins by the innate immune system, further reducing the synthesis of serotonin and consolidating the depressive process. We discuss the evidence showing that this process can be initiated by either interleukin stimulated by an infection or some vaccines or excessive psychological stress that activates the HPA axis together with said innate immune response, causing a process of aseptic inflammation in the central nervous system.


Assuntos
Depressão , Sistema Hipófise-Suprarrenal , Serotonina , Neuroglia , Interleucina-6 , Interferon gama , Interleucina-10 , Interleucina-1beta , Sistema Imunitário , Imunidade Inata , Sistema Nervoso
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