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Antipsychotic dopamine glutamate

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https://www.readbyqxmd.com/read/28956340/pde-inhibitors-for-the-treatment-of-schizophrenia
#1
Gretchen L Snyder, Kimberly E Vanover
Schizophrenia is a pervasive neuropsychiatric disorder affecting over 1% of the world's population. Dopamine system dysfunction is strongly implicated in the etiology of schizophrenia. Data support the long-standing concept of schizophrenia as a disease characterized by hyperactivity within midbrain (striatal D2) dopamine systems. In addition, there is now considerable evidence that glutamate neurotransmission, mediated through NMDA-type receptors, is deficient in patients with schizophrenia and that hypoactivity in cortical dopamine and glutamate pathways is a key feature of this serious mental disorder...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28953788/benzodiazepines-in-combination-with-antipsychotic-drugs-for-schizophrenia-gaba-ergic-targeted-therapy
#2
Adam Włodarczyk, Joanna Szarmach, Wiesław Jerzy Cubała, Mariusz Stanisław Wiglusz
Antipsychotics are a key intervention strategy in pharmacotherapy of schizophrenia. However, benzodiazepines are often prescribed to control sleep disturbances, anxiety or behavioural disinhibition. There is clinical evidence for the beneficial effect of the combined treatment of antipsychotics and benzodiazepines resulting in more favorable treatment outcome in schizophrenia with regard to positive and negative symptoms. This clinical phenomenon seems to be associated with the GABA-ergic activit ythat is believed to be disrupted in the schizophrenia and direct benzodiazepines effect on GABA-A receptors...
September 2017: Psychiatria Danubina
https://www.readbyqxmd.com/read/28881851/the-involvement-of-darpp-32-in-the-pathophysiology-of-schizophrenia
#3
REVIEW
Haitao Wang, Mohd Farhan, Jiangping Xu, Philip Lazarovici, Wenhua Zheng
Schizophrenia is one of the most devastating heterogeneous psychiatric disorders. The dopamine hypothesis is the longest standing pathoetiologic theory of schizophrenia based on neurochemical evidences of elevated brain striatal dopamine synthesis capacity and increased dopamine release in response to stress. Dopamine and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000 (DARPP-32) is a cytosolic protein highly enriched in the medium spiny neurons of the neostriatum, considered as the most important integrator between the cortical input and the basal ganglia, and associated with motor control...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28818421/erbb-signaling-antagonist-ameliorates-behavioral-deficit-induced-by-phencyclidine-pcp-in-mice-without-affecting-metabolic-syndrome-markers
#4
Hagar Tadmor, Idit Golani, Ravid Doron, Ilana Kremer, Alon Shamir
Schizophrenia is a severe syndrome that affects about 1% of the world population. Since the mid-1950s, antipsychotics have been used to treat schizophrenia with preference for treating positive symptoms; however, their tolerance level is low, there are numerous side effects, and only some patients respond to the treatment. Antipsychotic medications that are more effective, better tolerated, and with fewer adverse effects are urgently needed. Given the accumulating evidence of the role filled by the ErbB signaling network in the biology of the dopamine, GABA, and glutamate systems, and in the etiology of schizophrenia, we hypothesized that the ErbB network is a candidate for development of a novel agent through which various symptoms of schizophrenia and other psychiatric disorders might be treated...
August 14, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28790021/deficient-striatal-adaptation-in-aminergic-and-glutamatergic-neurotransmission-is-associated-with-tardive-dyskinesia-in-non-human-primates-exposed-to-antipsychotic-drugs
#5
Catherine Lévesque, Giovanni Hernandez, Souha Mahmoudi, Frédéric Calon, Fabrizio Gasparini, Baltazar Gomez-Mancilla, Pierre J Blanchet, Daniel Lévesque
Tardive dyskinesia (TD) is a potentially disabling condition encompassing all delayed, persistent, and often irreversible abnormal involuntary movements arising in a fraction of subjects during long-term exposure to centrally acting dopamine receptor-blocking agents such as antipsychotic drugs and metoclopramide. However, the pathogenesis of TD has proved complex and remains elusive. To investigate the mechanism underlying the development of TD, we have chronically exposed 17 Cebus apella monkeys to typical (11) or atypical (6) antipsychotic drugs...
October 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28756461/adolescent-stress-leads-to-glutamatergic-disturbance-through-dopaminergic-abnormalities-in-the-prefrontal-cortex-of-genetically-vulnerable-mice
#6
Yurie Matsumoto, Minae Niwa, Akihiro Mouri, Yukihiro Noda, Takeshi Fukushima, Norio Ozaki, Toshitaka Nabeshima
BACKGROUND: Stress during the adolescent period influences postnatal maturation and behavioral patterns in adulthood. Adolescent stress-induced molecular and functional changes in neurons are the key clinical features of psychiatric disorders including schizophrenia. OBJECTIVE: In the present study, we exposed genetically vulnerable mice to isolation stress to examine the molecular changes in the glutamatergic system involving N-methyl-d-aspartate (NMDA) receptors via dopaminergic disturbance in the prefrontal cortex (PFc)...
October 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28487497/the-involvement-of-darpp-32-in-the-pathophysiology-of-schizophrenia
#7
REVIEW
Haitao Wang, Mohd Farhan, Jiangping Xu, Philip Lazarovici, Wenhua Zheng
Schizophrenia is one of the most devastating heterogeneous psychiatric disorders. The dopamine hypothesis is the longest standing pathoetiologic theory of schizophrenia based on neurochemical evidences of elevated brain striatal dopamine synthesis capacity and increased dopamine release in response to stress. Dopamine and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000 (DARPP-32) is a cytosolic protein highly enriched in the medium spiny neurons of the neostriatum, considered as the most important integrator between the cortical input and the basal ganglia, and associated with motor control...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28358303/a-novel-bio-psychosocial-behavioral-treatment-model-in-schizophrenia
#8
REVIEW
Yong-Ku Kim, Joonho Choi, Seon-Cheol Park
Despite the substantial burden of illness in schizophrenia, there has been a discrepancy between the beneficial effects of an increased use of antipsychotic medications and achieving limited recovery or remission. Because the focus of the most common antipsychotic medications is on dopamine, which is associated with positive symptoms, there is an unmet need for patients with negative symptoms. Since cognitive and negative symptoms rather than positive symptoms are more closely associated with psychosocial impairments in patients with schizophrenia, the non-dopaminergic systems including glutamate and γ-aminobutyric acid (GABA) of the prefrontal cortex should be of concern as well...
March 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28272861/analysis-of-the-glutamate-agonist-ly404-039-binding-to-nonstatic-dopamine-receptor-d2-dimer-structures-and-consensus-docking
#9
Ramin Ekhteiari Salmas, Philip Seeman, Busecan Aksoydan, Ismail Erol, Isik Kantarcioglu, Matthias Stein, Mine Yurtsever, Serdar Durdagi
Dopamine receptor D2 (D2R) plays an important role in the human central nervous system and is a focal target of antipsychotic agents. The D2(High)R and D2(Low)R dimeric models previously developed by our group are used to investigate the prediction of binding affinity of the LY404,039 ligand and its binding mechanism within the catalytic domain. The computational data obtained using molecular dynamics simulations fit well with the experimental results. The calculated binding affinities of LY404,039 using MM/PBSA for the D2(High)R and D2(Low)R targets were -12...
March 22, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28235555/re-arrangements-of-gene-transcripts-at-glutamatergic-synapses-after-prolonged-treatments-with-antipsychotics-a-putative-link-with-synaptic-remodeling
#10
Elisabetta Filomena Buonaguro, Felice Iasevoli, Federica Marmo, Anna Eramo, Gianmarco Latte, Camilla Avagliano, Carmine Tomasetti, Andrea de Bartolomeis
OBJECTIVES: The postsynaptic density (PSD) represents a site of dopamine-glutamate integration. Despite multiple evidence of PSD involvement in antipsychotic-induced synaptic changes, there are no direct head-to-head comparisons of the effects at the PSD of antipsychotics with different receptor profile and at different doses after chronic administration. METHODS: Molecular imaging of gene expression was used to investigate whether chronic treatment with first and second generation antipsychotics (haloperidol, asenapine and olanzapine) may induce changes in the expression levels of PSD transcripts involved in schizophrenia pathophysiology, i...
February 22, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/27981352/the-clinical-heterogeneity-of-drug-induced-myoclonus-an-illustrated-review
#11
REVIEW
Sabine Janssen, Bastiaan R Bloem, Bart P van de Warrenburg
A wide variety of drugs can cause myoclonus. To illustrate this, we first discuss two personally observed cases, one presenting with generalized, but facial-predominant, myoclonus that was induced by amantadine; and the other presenting with propriospinal myoclonus triggered by an antibiotic. We then review the literature on drugs that may cause myoclonus, extracting the corresponding clinical phenotype and suggested underlying pathophysiology. The most frequently reported classes of drugs causing myoclonus include opiates, antidepressants, antipsychotics, and antibiotics...
August 2017: Journal of Neurology
https://www.readbyqxmd.com/read/27833522/histamine-h3-receptors-and-its-antagonism-as-a-novel-mechanism-for-antipsychotic-effect-a-current-preclinical-clinical-perspective
#12
REVIEW
Danish Mahmood
Histamine H3 receptors are present as autoreceptors on histaminergic neurons and as heteroreceptors on nonhistaminergic neurones. They control the release and synthesis of histamine and several other key neurotransmitters in the brain. H3 antagonism may be a novel approach to develop a new class of antipsychotic medications given the gathering evidence reporting therapeutic efficacy in several central nervous system disorders. Several medications such as cariprazine, lurasidone, LY214002, bexarotene, rasagiline, raloxifene, BL-1020 and ITI-070 are being developed to treat the negative symptoms and cognitive impairments of schizophrenia...
October 2016: International Journal of Health Sciences
https://www.readbyqxmd.com/read/27692238/heterogeneity-in-dopamine-neuron-synaptic-actions-across-the-striatum-and-its-relevance-for-schizophrenia
#13
REVIEW
Nao Chuhma, Susana Mingote, Abigail Kalmbach, Leora Yetnikoff, Stephen Rayport
Brain imaging has revealed alterations in dopamine uptake, release, and receptor levels in patients with schizophrenia that have been resolved on the scale of striatal subregions. However, the underlying synaptic mechanisms are on a finer scale. Dopamine neuron synaptic actions vary across the striatum, involving variations not only in dopamine release but also in dopamine neuron connectivity, cotransmission, modulation, and activity. Optogenetic studies have revealed that dopamine neurons release dopamine in a synaptic signal mode, and that the neurons also release glutamate and gamma-aminobutyric acid as cotransmitters, with striking regional variation...
January 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/27690134/induced-obsessive-compulsive-symptoms-ocs-in-schizophrenia-patients-under-atypical-2-antipsychotics-aaps-review-and-hypotheses
#14
REVIEW
Diane Grillault Laroche, Adeline Gaillard
The prevalence of OCS and OCD is higher in schizophrenic patients than in the general population. These disorders are sometimes induced by AAPs. There is higher frequency of OCS and greater severity in patients treated with antipsychotics with predominant anti-serotoninergic profiles opposed to those with predominant dopaminergic blockade. Induced OCS may be due to complex neuromodulation involving many serotonin, dopamine and glutamate receptors and several subtypes. Concerning connectivity, AAPs differentially influence the BOLD signal, depending on the intensity of D2 receptor blockade...
December 30, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27633376/improving-current-treatments-for-schizophrenia
#15
REVIEW
Nadja P Maric, Milica J Jovicic, Marina Mihaljevic, Cedo Miljevic
Preclinical Research After the identification of the schizophrenia as an illness over a century ago, treatment of affected individuals included unspecific, mostly very robust methods including deep insulin coma and lobectomy/leucotomy. The first relatively specific treatment of schizophrenia started about 60 years ago with the antipsychotic chlorpromazine. All currently approved antipsychotic drugs block dopamine receptors, indicating that manipulation of dopaminergic function is fundamental to a therapeutic response in psychosis...
November 2016: Drug Development Research
https://www.readbyqxmd.com/read/27550734/protein-markers-of-neurotransmitter-synthesis-and-release-in-postmortem-schizophrenia-substantia-nigra
#16
Kirsten E Schoonover, Lesley A McCollum, Rosalinda C Roberts
The substantia nigra (SN) provides the largest dopaminergic input to the brain, projects to the striatum (the primary locus of action for antipsychotic medication), and receives GABAergic and glutamatergic inputs. This study used western blot analysis to compare protein levels of tyrosine hydroxylase (TH), glutamate decarboxylase (GAD67), and vesicular glutamate transporters (vGLUT1 and vGLUT2) in postmortem human SN in schizophrenia subjects (n=13) and matched controls (n=12). As a preliminary analysis, the schizophrenia group was subdivided by (1) treatment status: off medication (n=4) or on medication (n=9); or (2) treatment response: treatment resistant (n=5) or treatment responsive (n=4)...
January 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27536115/cycloid-psychoses-in-the-psychosis-spectrum-evidence-for-biochemical-differences-with-schizophrenia
#17
Nora Wa van de Kerkhof, Durk Fekkes, Frank Mma van der Heijden, Witte Jg Hoogendijk, Gerald Stöber, Jos Im Egger, Willem Ma Verhoeven
Cycloid psychoses (CP) differ from schizophrenia regarding symptom profile, course, and prognosis and over many decades they were thought to be a separate entity within the psychosis spectrum. As to schizophrenia, research into the pathophysiology has focused on dopamine, brain-derived neurotrophic factor, and glutamate signaling in which, concerning the latter, the N-methyl-d-aspartate receptor plays a crucial role. The present study aims to determine whether CP can biochemically be delineated from schizophrenia...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27469238/pharmacogenetics-of-tardive-dyskinesia-an-updated-review-of-the-literature
#18
REVIEW
Rachel K Lanning, Clement C Zai, Daniel J Müller
Tardive dyskinesia (TD) is a serious and potentially irreversible side effect of long-term exposure to antipsychotic medication characterized by involuntary trunk, limb and orofacial muscle movements. Various mechanisms have been proposed for the etiopathophysiology of antipsychotic-induced TD in schizophrenia patients with genetic factors playing a prominent role. Earlier association studies have focused on polymorphisms in CYP2D6, dopamine-, serotonin-, GABA- and glutamate genes. This review highlights recent advances in the genetic investigation of TD...
August 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27465045/neurochemical-and-behavioral-studies-on-the-5-ht1a-dependent-antipsychotic-action-of-the-mglu4-receptor-agonist-lsp4-2022
#19
Monika Woźniak, Krystyna Gołembiowska, Karolina Noworyta-Sokołowska, Francine Acher, Paulina Cieślik, Magdalena Kusek, Krzysztof Tokarski, Andrzej Pilc, Joanna M Wierońska
LSP4-2022 is a novel, orthosteric agonist of mGlu4 receptor that induces antipsychotic-like activity in animal studies. In the present study, the involvement of 5-HT1A receptors in LSP4-2022-induced antipsychotic actions and the neurochemical background of that interaction were investigated. In several behavioral tests the actions of effective doses of the compound (0.5-2 mg/kg) were antagonized via the administration of the 5-HT1A antagonist WAY100635 (0.1 mg/kg). The co-administration of sub-effective dose of the 5-HT1A agonist (R)-(S)-8-OH-DPAT (0...
March 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27272046/pharmacogenetic-study-of-antipsychotic-induced-acute-extrapyramidal-symptoms-in-a-first-episode-psychosis-cohort-role-of-dopamine-serotonin-and-glutamate-candidate-genes
#20
MULTICENTER STUDY
S Mas, P Gassó, A Lafuente, M Bioque, A Lobo, A Gonzàlez-Pinto, M S Olmeda, I Corripio, A Llerena, B Cabrera, J Saiz-Ruiz, M Bernardo
This study investigated whether the risk of presenting antipsychotic (AP)-induced extrapyramidal symptoms (EPS) could be related to single-nucleotide polymorphisms (SNPs) in a naturalistic cohort of first episode psychosis (FEP) patients. Two hundred and two SNPs in 31 candidate genes (involved in dopamine, serotonin and glutamate pathways) were analyzed in the present study. One hundred and thirteen FEP patients (43 presenting EPS and 70 non-presenting EPS) treated with high-potency AP (amisulpride, paliperidone, risperidone and ziprasidone) were included in the analysis...
October 2016: Pharmacogenomics Journal
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