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Alzheimer antidepressants

Rona R Ramsay, Alen Albreht
Monoamine oxidases (MAOs) catalyse the oxidation of neurotransmitter amines and a wide variety of primary, secondary and tertiary amine xenobiotics, including therapeutic drugs. While inhibition of MAO activity in the periphery removes protection from biogenic amines and so is undesirable, inhibition in the brain gives vital antidepressant and behavioural advantages that make MAO a major pharmaceutical target for inhibitor design. In neurodegenerative diseases, MAO inhibitors can help to maintain neurotransmitter levels, making it a common feature in novel multi-target combinations designed to combat Alzheimer's disease, albeit not yet proven clinically...
March 7, 2018: Journal of Neural Transmission
Filippo Caraci, Simona Federica Spampinato, Maria Grazia Morgese, Fabio Tascedda, Maria Grazia Salluzzo, Maria Concetta Giambirtone, Giuseppe Caruso, Antonio Munafò, Sebastiano Alfio Torrisi, Gian Marco Leggio, Luigia Trabace, Ferdinando Nicoletti, Filippo Drago, Maria Angela Sortino, Agata Copani
In the last several years a large number of studies have demonstrated the neurobiological and clinical continuum between depression and Alzheimer's disease (AD). Depression is a risk factor for the development of AD, and the presence of depressive symptoms significantly increases the conversion of Mild Cognitive Impairment (MCI) into AD. Common pathophysiological events have been identified in depression and AD, including neuroinflammation with an aberrant Tumor Necrosis Factor-α (TNF-α) signaling, and an impairment of Brain-Derived Neurotrophic Factor (BDNF) and Transforming-Growth-Factor-β1 (TGF-β1) signaling...
February 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Nina Z Xu, Margot Ernst, Marco Treven, Rok Cerne, Mark Wakulchik, Xia Li, Timothy M Jones, Scott D Gleason, Denise Morrow, Jeffrey M Schkeryantz, Md Toufiqur Rahman, Guanguan Li, Michael M Poe, James M Cook, Jeffrey M Witkin
RATIONALE: Associated with frank neuropathology, patients with Alzheimer's disease suffer from a host of neuropsychiatric symptoms that include depression, apathy, agitation, and aggression. Negative allosteric modulators (NAMs) of α5-containing GABAA receptors have been suggested to be a novel target for antidepressant action. We hypothesized that pharmacological modulation of this target would engender increased motivation in stressful environments. METHODS: We utilized electrophysiological recordings from Xenopus oocytes and behavioral measures in mice to address this hypothesis...
January 26, 2018: Psychopharmacology
Philipp Hessmann, Richard Dodel, Erika Baum, Matthias J Müller, Greta Paschke, Bernhard Kis, Jan Zeidler, Mike Klora, Jens-Peter Reese, Monika Balzer-Geldsetzer
OBJECTIVE: The use of antidepressant drugs in dementia patients is associated with the risk of adverse events, and the evidence for relevant effects is scarce. We aimed to determine the associations between the prescription of antidepressants and patients' sociodemographic (e.g., age, gender, living situation) and clinical characteristics (e.g., disease severity, neuropsychiatric symptoms). MATERIALS AND METHODS: We included 395 institutionalized and community-dwelling patients with Alzheimer's disease (AD) across all severity stages of dementia in a cross-sectional study design...
March 2018: International Journal of Clinical Pharmacology and Therapeutics
Luca Settimo, David Taylor
Trazodone is a drug that was introduced in the clinic almost 40 years ago. It is licensed to treat depression, but it is also commonly used off-label to treat insomnia. A recent study shows that it could be promising in preventing neurodegeneration in mice, and clinical trials to assess its possible beneficial effects on dementia and Alzheimer's disease are expected to start soon in humans. In this study, we describe the dose-dependent pharmacology of trazodone by carrying out pharmacokinetic simulations aiming to predict the brain concentrations of trazodone for different drug-dosing regimens and calculating occupancy for 28 different targets for which published trazodone-binding data are available...
January 2018: Journal of Psychopharmacology
Simone Carradori, Daniela Secci, Jacques P Petzer
Monoamine oxidase (MAO) inhibitors, after the initial 'golden age', are currently used as third-line antidepressants (selective MAO-A inhibitors) or clinically enrolled as co-adjuvants for neurodegenerative diseases (selective MAO-B inhibitors). However, the research within this field is always increasing due to their pivotal role in modulating synaptic functions and monoamines metabolism. Areas covered: In this paper, MAO inhibitors (2015-2017) are disclosed ordering all the patents according to their chemical scaffold...
January 17, 2018: Expert Opinion on Therapeutic Patents
Claudia Bartels, Michael Wagner, Steffen Wolfsgruber, Hannelore Ehrenreich, Anja Schneider
OBJECTIVE: Depression is associated with an increased risk of Alzheimer's disease. Research has shown that the selective serotonin reuptake inhibitor (SSRI) citalopram decreases amyloid-β generation and plaque load. The authors evaluated the impact of SSRI treatment on CSF biomarkers and progression from mild cognitive impairment (MCI) to Alzheimer's dementia. METHOD: Data sets from 755 currently nondepressed participants from the longitudinal Alzheimer's Disease Neuroimaging Initiative were evaluated by Kaplan-Meier analysis and analyses of variance and covariance with ApoE4 status and age as covariates...
March 1, 2018: American Journal of Psychiatry
Hamzah Bakouni, Djamal Berbiche, Helen-Maria Vasiliadis
BACKGROUND: Given the common off-label use of antipsychotics (AP), we aimed to assess the factors associated with this use in community living older adults. METHODS: The study sample consisted of a large representative sample of older adults (n = 4108), covered under a public drug insurance plan in Canada. Off-label use of antipsychotics was defined by the absence of an approved indication for this use, according to Health Canada's drug product database. Multinomial logistic regression was used to assess the factors associated with off-label use...
November 20, 2017: Aging & Mental Health
Cong Lu, Liming Dong, Jingwei Lv, Yan Wang, Bei Fan, Fengzhong Wang, Xinmin Liu
20(S)-protopanaxadiol (PPD) possesses various biological properties, including anti-inflammatory, antitumor and anti-fatigue properties. Recent studies found that PPD functioned as a neurotrophic agent to ameliorate the sensory deficit caused by glutamate-induced excitotoxicity through its antioxidant effects and exhibited strong antidepressant-like effects in vivo. The objective of the present study was first to investigate the effect of PPD in scopolamine (SCOP)-induced memory deficit in mice and the potential mechanisms involved...
January 5, 2018: Chemico-biological Interactions
Robert F Bruns, Stephen N Mitchell, Keith A Wafford, Alex J Harper, Elaine A Shanks, Guy Carter, Michael J O'Neill, Tracey K Murray, Brian J Eastwood, John M Schaus, James P Beck, Junliang Hao, Jeffrey M Witkin, Xia Li, Eyassu Chernet, Jason S Katner, Hong Wang, John W Ryder, Meghane E Masquelin, Linda K Thompson, Patrick L Love, Deanna L Maren, Julie F Falcone, Michelle M Menezes, Linli Zhang, Charles R Yang, Kjell A Svensson
DETQ, an allosteric potentiator of the dopamine D1 receptor, was tested in therapeutic models that were known to respond to D1 agonists. Because of a species difference in affinity for DETQ, all rodent experiments used transgenic mice expressing the human D1 receptor (hD1 mice). When given alone, DETQ reversed the locomotor depression caused by a low dose of reserpine. DETQ also acted synergistically with L-DOPA to reverse the strong hypokinesia seen with a higher dose of reserpine. These results indicate potential as both monotherapy and adjunct treatment in Parkinson's disease...
January 2018: Neuropharmacology
Zhang Wei, Guo Junhong, Niu Xiaoyuan, Wang Jie, Wang Zhaojun, Wu Meina, Yang Wei, Zhang Jun, Qi Jinshun
Alzheimer's disease (AD) is the primary cause of dementia. There is no effective treatment. Amyloid-β peptide (Aβ) plays an important role in the pathogenesis and thus strategies suppressing Aβ production and accumulation seem promising. Citalopram is an antidepressant drug and can decrease Aβ production and amyloid plaques in transgenic mice of AD and humans. Whether citalopram can ameliorate memory deficit was not known yet. We tested the effects of citalopram on behavioral performance and synaptic plasticity in female 3xTgAD mice, a well-characterized model of AD...
2017: BioMed Research International
Miaomiao Jia, Chenxin Li, Ying Zheng, Xiaojing Ding, Meng Chen, Jianhua Ding, Renhong Du, Ming Lu, Gang Hu
Background: Leonurine is an active alkaloid that is extracted from Traditional Chinese Medicine Herba leonuri. Emerging evidence indicates that leonurine produces neuroprotective effects in ischemic stroke, Parkinson's disease, and Alzheimer's disease. However, the effect of leonurine in neuropsychiatric disorders, especially in major depression, remains unknown. Methods: We used the chronic mild stress mouse model to explore the antidepressant effects of leonurine and the potential mechanisms...
November 1, 2017: International Journal of Neuropsychopharmacology
Haider Behbehani, Kamal M Dawood, Thoraya A Farghaly
Several natural products containing benzosuberone moiety are clinically reported as anti-tumor agents. Furthermore, several synthetic benzosuberones cited in this review exhibited wide range of theraputic activities such as bacteriostatic, anti-inflammatory, antidepressants and anti-tumor activities. Our recent review provides an overview of the different methods to synthesize the benzosuberones and their extensive biological activities. Areas covered: Thirty-two patents among 130 references are cited in this review that covered the recent inhibitory activities of the benzosuberone scaffolds and their broad area of biological applications up to the first quarter of 2017...
January 2018: Expert Opinion on Therapeutic Patents
Klaas van der Spek, Raymond Tcm Koopmans, Martin Smalbrugge, Marjorie Hjmg Nelissen-Vrancken, Roland B Wetzels, Claudia Hw Smeets, Steven Teerenstra, Sytse U Zuidema, Debby L Gerritsen
BACKGROUND: We studied the patient and non-patients factors of inappropriate psychotropic drug (PD) prescription for neuropsychiatric symptoms (NPS) in nursing home patients with severe dementia. METHODS: In a cross-sectional study, the appropriateness of prescriptions was explored using the Appropriate Psychotropic drug use In Dementia (APID) index sum score. This index assesses information from medical records on indication, evaluation, dosage, drug-drug interactions, drug-disease interactions, duplications, and therapy duration...
September 21, 2017: International Psychogeriatrics
Dong-Sheng Sun, Li-Feng Gao, Li Jin, Hao Wu, Qun Wang, You Zhou, Shuhao Fan, Xia Jiang, Dan Ke, Hao Lei, Jian-Zhi Wang, Gong-Ping Liu
Fluoxetine (FLX) has broad neurobiological functions and neuroprotective effects; however, the preventive effects of FLX on cognitive impairments in Alzheimer's disease (AD) have not been reported. Here, we studied whether adolescent administration of fluoxetine can prevent memory deficits in AD transgenic mice that harbour PS1m146v, APPswe and TauP301L mutations (3 × TgAD). FLX was applied through peritoneal injection to the mice at postnatal day 35 (p35) for 15 consecutive days, and the effects of FLX were observed at 6-month...
September 11, 2017: Neuropharmacology
Fiachra J Maguire, Isabelle Killane, Andrew P Creagh, Orna Donoghue, Rose Anne Kenny, Richard B Reilly
OBJECTIVES: Slow gait has been shown to be a good predictor of declining cognitive function in healthy older adults. Motoric cognitive risk (MCR) syndrome is a new construct incorporating slow gait and subjective cognitive complaints in individuals without dementia who have preserved activities of daily living. This analysis investigated the prevalence of MCR and factors associated with MCR in a nationally representative population. In addition, cross-sectional associations between MCR and cognitive domains, an relationship yet to be fully elucidated in literature, was investigated...
September 9, 2017: Journal of the American Medical Directors Association
Christoph Mueller, Jonathan Huntley, Brendon Stubbs, Andrew Sommerlad, André F Carvalho, Gayan Perera, Robert Stewart, Nicola Veronese
OBJECTIVE: Depression is associated with increased mortality in community samples. The use of antidepressant medication may also increase mortality, however, it is still unclear whether taking antidepressants before or after a diagnosis of dementia influences survival. DESIGN: Retrospective. SETTING: A cohort with a diagnosis of Alzheimer disease (AD) from a large mental health and dementia care database in South London, linked to hospitalization and mortality data...
August 31, 2017: Journal of the American Medical Directors Association
Madeleine Monique Uys, Mohammed Shahid, Brian Herbert Harvey
α2A- and α2C-adrenoceptors (ARs) are the primary α2-AR subtypes involved in central nervous system (CNS) function. These receptors are implicated in the pathophysiology of psychiatric illness, particularly those associated with affective, psychotic, and cognitive symptoms. Indeed, non-selective α2-AR blockade is proposed to contribute toward antidepressant (e.g., mirtazapine) and atypical antipsychotic (e.g., clozapine) drug action. Both α2C- and α2A-AR share autoreceptor functions to exert negative feedback control on noradrenaline (NA) release, with α2C-AR heteroreceptors regulating non-noradrenergic transmission (e...
2017: Frontiers in Psychiatry
Justyna Brodowicz, Edmund Przegaliński, Christian P Müller, Malgorzata Filip
Correlational and causal comparative research link ceramide (Cer), the precursor of complex sphingolipids, to some psychiatric (e.g., depression, schizophrenia (SZ), alcohol use disorder, and morphine antinociceptive tolerance) and neurological (e.g., Alzheimer's disease (AD), Parkinson disease (PD)) disorders. Cer generation can occur through the de novo synthesis pathway, the sphingomyelinase pathways, and the salvage pathway. The discoveries that plasma Cer concentration increase during depressive episodes in patients and that tricyclic and tetracyclic antidepressants functionally inhibit acid sphingomyelinase (ASM), the enzyme that catalyzes the degradation of sphingomyelin to Cer, have initiated a series of studies on the role of the ASM-Cer system in depressive disorder...
August 25, 2017: Neurotoxicity Research
Vitor Prates Lorenzo, Mateus Feitosa Alves, Luciana Scotti, Socrates Golzio Dos Santos, Margareth de Fatima Formiga Melo Diniz, Marcus Tullius Scotti
Cissampelos sympodialis Eichl is used in folk medicine for the treatment of various inflammatory diseases; several alkaloids have been isolated from this species and some of them have anti-allergic, immunomodulatory and spasmolytic activities. Treatment of rats with the total tertiary alkaloid fraction showed an antidepressant effect. One of the depression causes can be the deficiency of monoamines, which is a factor displayed in patients with Alzheimer's disease. Theoretical studies using in silico methods have aided in the process of drug discovery...
2017: Current Topics in Medicinal Chemistry
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