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New antidepressants

Beata Powroźnik, Karolina Słoczyńska, Krzysztof Marciniec, Paweł Zajdel, Elżbieta Pękala
Purpose: Determination of the mutagenic potential of new biologically active compounds is of great concern for preliminary toxicity testing and drug development. Methods: The mutagenic and antimutagenic effects of some quinoline- and isoquinolinesulfonamide analogs of aripiprazole (1-8), which display potent antidepressant, anxiolytic, and antipsychotic properties, were evaluated using the Vibrio harveyi assay and OSIRIS Property Explorer software. Additionally, the Ames test was used as the reference. Results: In silico prediction showed that compounds 5 (N-(3-(4-(2,3- dichlorophenyl)piperazin-1-yl)propyl)quinoline-7-sulfonamide) and 6 (N-(4-(4-(2,3- Dichlorophenyl)piperazin-1-yl)butyl)quinoline-7-sulfonamide) trigger a mutagenic structural alert...
September 2016: Advanced Pharmaceutical Bulletin
Nan Sook Park, Yuri Jang, David A Chiriboga
OBJECTIVES: Despite a high prevalence of mental health problems, racial/ethnic minorities are often reluctant to seek mental health services. Their reluctance may be shaped by cultural beliefs and stigma about mental health. The present study examined how beliefs and stigma about depression (e.g. disbelief in depression as a health-related condition, perception of depression as a normal part of aging, and/or depression as a sign of personal weakness/family shame) pose barriers to older Korean Americans' willingness to use mental health counseling and antidepressants...
October 21, 2016: Ethnicity & Health
V A Doss, Dharaniyambigai Kuberapandian
BACKGROUND: The objective of this study is to develop a new animal model based on signaling pathways to understand the pathophysiology, therapy of depression, and to investigate the antidepressant activity of Enicostemma littorale which is not yet established. METHODS: Animal models of depression were raised by physical methods and administration of methyl isobutyl ketone (100 mg/kg b.w., i.p.,) and a protein tyrosine phosphatase inhibitor, sodium orthovanadate (30 mg/kg b...
2016: International Journal of Preventive Medicine
Mariusz Papp, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Paul Willner
Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action...
October 18, 2016: Behavioural Pharmacology
Virgil Radu Enatescu, Ion Papava, Ileana Enatescu, Mirela Antonescu, Andrei Anghel, Edward Seclaman, Ioan Ovidiu Sirbu, Catalin Marian
OBJECTIVE: Significant progress was made in the understanding etiopathogenic factors related to MDD, including through research on the role of micro RNAs (miRs). We investigated plasma miRs as potential markers for MDD in patients treated with antidepressants. METHODS: At the initiation and at the end of twelve weeks of treatment, blood samples were collected and a structured diagnostic interview and a standardized depression rating scale for the presence and severity of major depression were done...
September 2016: Psychiatry Investigation
Hsin-An Chang, Ying-Hsiu Wang, Che-Se Tung, Chin-Bin Yeh, Yia-Ping Liu
OBJECTIVE: Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), play important roles in treating depression. In this experiment, we examined whether 7,8-dihydroxyflavone, a novel potent TrkB agonist, could reverse the behavioral and biochemical abnormalities induced by the chronic mild stress (CMS) paradigm in rats. METHODS: SD rats were exposed to a battery of stressors for 56 days. 7,8-dihydroxyflavone (5 and 20 mg/kg) were administered intraperitoneally during the last 28 days of the CMS paradigm...
September 2016: Psychiatry Investigation
Orjan Skogar, Johan Lokk
This review focuses on the diagnosis and management of Parkinson-related pain which is one of the more frequently reported nonmotor symptoms in Parkinson's disease (PD), which is the second most common neurodegenerative disease after Alzheimer's disease. Pain is ranked high by patients as a troublesome symptom in all stages of the disease. In early-stage PD, pain is rated as the most bothersome symptom. Knowledge of the correct diagnosis of pain origin and possible methods of treatments for pain relief in PD is of great importance...
2016: Journal of Multidisciplinary Healthcare
Angelo Alonzo, Scott Aaronson, Marom Bikson, Mustafa Husain, Sarah Lisanby, Donel Martin, Shawn M McClintock, William M McDonald, John O'Reardon, Zeinab Esmailpoor, Colleen Loo
Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5mA, 20 sessions of 30min duration over 4weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase...
October 15, 2016: Contemporary Clinical Trials
Mikkel Vestergaard Olesen, Gitta Wörtwein, Jonas Folke, Bente Pakkenberg
Electroconvulsive stimulation (ECS) is one of the strongest stimulators of hippocampal neurogenesis in rodents that represents a plausible mechanism for the efficacy of electroconvulsive therapy (ECT) in major depressive disorder. Using design-based stereological cell counting, we recently documented an initial 2.6-fold increase in neurogenesis following a clinical relevant schedule of ECS, a treatment also rescuing depression-like behavior in rats. However, these results gave no demonstration of the longevity of newly-generated neurons...
October 18, 2016: Hippocampus
Chouki Chenaf, Eric Chapuy, Frédéric Libert, Fabien Marchand, Christine Courteix, Marianne Bertrand, Cecilia Gabriel, Elisabeth Mocaër, Alain Eschalier, Nicolas Authier
Antidepressants are first-line treatments of neuropathic pain but not all of these drugs are really effective. Agomelatine is an antidepressant with a novel mode of action, acting as a MT1/MT2 melatonergic receptor agonist and a 5-HT2C receptor antagonist that involves indirect noradrenaline release. Melatonin, serotonin and noradrenaline have been involved in the pathophysiology of neuropathic pain. Yet no study has been conducted to determine agomelatine effects on neuropathic pain in animal models.Using three rat models of neuropathic pain of toxic (oxaliplatin/OXA), metabolic (streptozocin/STZ) and traumatic (sciatic nerve ligation/CCI) etiologies, we investigated the anti-hypersensitivity effect of acute and repeated agomelatine administration...
October 1, 2016: Pain
Sudipta Saha, Vinit Raj, Amit Rai
The chemistry of heterocyclic containing, 1,3,4-thiadiazole has been an interesting field of study from ancient years. Subsequently, 1,3,4-thiadiazole nucleus constitutes a significant class of compounds for new drug development. Recently, various 1,3,4-thiadiazole derivatives have been synthesized and evaluated their biological activities including antimicrobial, antituberculosis, antioxidant, anti-inflammatory, anticonvulsants, antidepressant and anxiolytic, antihypertensive, anticancer and antifungal activity...
October 13, 2016: Anti-cancer Agents in Medicinal Chemistry
Danielle Macedo, Adriano José Maia Chaves Filho, Caren Nádia Soares de Sousa, João Quevedo, Tatiana Barichello, Hélio Vitoriano Nobre Júnior, David Freitas de Lucena
OBJECTIVES: The first drug repurposed for the treatment of depression was the tuberculostatic iproniazid. At present, drugs belonging to new classes of antidepressants still have antimicrobial effects. Dysbiosis of gut microbiota was implicated in the development or exacerbation of mental disorders, such as major depressive disorder (MDD). Based on the current interest in the gut-brain axis, the focus of this narrative review is to compile the available studies regarding the influences of gut microbiota in behavior and depression and to show the antimicrobial effect of antidepressant drugs...
September 28, 2016: Journal of Affective Disorders
Christian Borch Jacobsen, Morten Meldal, Frederik Diness
A general method for transition metal-free N-arylation of amines has been developed. Mechanistic studies have revealed that the ability of the base to facilitate the desired amination without promoting unwanted side reactions is the guiding factor. By employing lithium bis(trimethylsilyl)amide as a base the resultant deprotonated amines readily react with a range of unactivated fluorobenzene derivatives. This new arylation method is utilized for the simple two-step synthesis of the antidepressant Vortioxetine...
October 14, 2016: Chemistry: a European Journal
Maria Jenelyn M Alviar, Tom Hale, Monalisa Dungca
BACKGROUND: This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP. OBJECTIVES: This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP...
October 14, 2016: Cochrane Database of Systematic Reviews
Prashant Singh, Braden Kuo
Nausea and vomiting result from continuous interactions among gastrointestinal, central nervous system, and autonomic nervous system. Despite being closely associated, central pathways of nausea and vomiting appear to be at least partly different and nausea is no longer considered only a penultimate step of vomiting. Although our understanding of central pathways of nausea has improved over the last one decade, it is still very basic. Afferent pathways from gastrointestinal tract via vagus, vestibular system, and chemoreceptor trigger zone project to nucleus tractus solitarius which, in turn, relays the signal to central pattern generator initiating multiple downstream pathways...
October 12, 2016: Current Treatment Options in Gastroenterology
Andrea Fagiolini, Giovanni Amodeo, Arianna Goracci, Patrizia Blardi
AIM: This paper examines the use of Trazodone Contramid® in major depressive disorder (MDD), with a focus on practical guidance regarding real world challenges. The paper includes clinical case reports, developed for didactic reasons, which detail the practical management with Trazodone Contramid® of patients with MDD and either insomnia or anxiety or dementia or isolated (ipo)manic symptoms, which often fulfill the criteria for a diagnosis of MDD with with anxious distress or MDD with mixed features, according to the new DSM-5 classification...
July 2016: Rivista di Psichiatria
Toshi A Furukawa, Andrea Cipriani, Lauren Z Atkinson, Stefan Leucht, Yusuke Ogawa, Nozomi Takeshima, Yu Hayasaka, Anna Chaimani, Georgia Salanti
BACKGROUND: Previous studies have shown that placebo response rates in antidepressant trials have been increasing since the 1970s. However, these studies have been based on outdated or limited datasets and have used inappropriate statistical methods. We did a systematic review of placebo-controlled randomised controlled trials of antidepressants to examine associations between placebo-response rates and study and patient characteristics. METHODS: In this systematic review, we searched for published and unpublished double-blind randomised placebo-controlled trials of first-generation and second-generation antidepressants for acute treatment of major depression in adults (update: Jan 8, 2016)...
October 7, 2016: Lancet Psychiatry
Steven F Grieco, Dmitry Velmeshev, Marco Magistri, Hagit Eldar-Finkelman, Mohammad A Faghihi, Richard S Jope, Eleonore Beurel
OBJECTIVES: We examined mechanisms that contribute to the rapid antidepressant effect of ketamine in mice that is dependent on glycogen synthase kinase-3 (GSK3) inhibition. METHODS: We measured serotonergic (5HT)-2C-receptor (5HTR2C) cluster microRNA (miRNA) levels in mouse hippocampus after administering an antidepressant dose of ketamine (10 mg/kg) in wild-type and GSK3 knockin mice, after GSK3 inhibition with L803-mts, and in learned helpless mice. RESULTS: Ketamine up-regulated cluster miRNAs 448-3p, 764-5p, 1264-3p, 1298-5p and 1912-3p (2- to 11-fold)...
October 10, 2016: World Journal of Biological Psychiatry
Qiuying Zhao, Xiaohui Wu, Shuo Yan, Xiaofang Xie, Yonghua Fan, Jinqiang Zhang, Cheng Peng, Zili You
BACKGROUND: Discoveries that microglia-mediated neuroinflammation is involved in the pathological process of depression provided a new strategy for novel antidepressant therapy. Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor regulating inflammation and microglial polarization and, therefore, a potential target for resolving depressive disorders. Our hypothesis was that antidepressant effects could be achieved through anti-inflammatory and neuroprotective activities by PPARγ-dependent microglia-modulating agents...
October 4, 2016: Journal of Neuroinflammation
Sarah Mello, Kieran A O'Connor
In recent years, 1,200 long-term care facility (LTCF) beds have been closed in Ireland, resulting in residents being transferred between facilities. The current study examined morbidity and mortality in residents relocated between LTCFs. The outcomes were studied for residents who transferred between LTCFs compared to residents who did not move (i.e., controls). A retrospective analysis was performed recording demographic data and markers of function and frailty. As a measure of morbidity, new antidepressant medication prescriptions and antibiotic drug use were examined...
October 5, 2016: Journal of Gerontological Nursing
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