Bleich, Stefan

[["dc.bibliographiccitation.firstpage","466"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Fortschritte der Neurologie · Psychiatrie"],["dc.bibliographiccitation.lastpage","475"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Maler, Manuel"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Degner, Detlef"],["dc.contributor.author","Rüther, Eckart"],["dc.date.accessioned","2017-09-07T11:44:45Z"],["dc.date.available","2017-09-07T11:44:45Z"],["dc.date.issued","2008"],["dc.description.abstract","The spectrum of action of flupirtine includes analgesic, muscle-relaxant and neuroprotective properties. The substance's mechanism of action has yet to be fully explained. Over the past few years, however, evidence has accumulated that flupirtine interacts with the glutamatergic N-Methyl-D-Aspartate (NMDA) receptor. Although it was not possible to demonstrate a direct effect on the NMDA receptor, all of the findings pointed to an indirect influence on the NMDA receptor in the sense of a functional NMDA antagonism. It was thus postulated that a site of action \"up- or downstream\" of the NMDA receptor is influenced. Such a site of action proved to be the G-protein-activated inwardly rectifying K+ channels (GIRK), the opening of which leads to a stabilisation of the resting membrane potential of neuronal cells and thus causes an indirect inhibition of the NMDA receptor. At therapeutically relevant concentrations, flupirtine is a neuronal potassium channel opener. This mechanism may explain the spectrum of action of flupirtine. Selective neuronal potassium channel opening (SNEPCO) thus proves to be a new principle of action, making flupirtine the prototype of a new substance class with analgesic, muscle-relaxant and neuroprotective properties. The experimental basis for this working hypothesis and the resulting model concepts are presented from the perspective of a four-stage approach."],["dc.description.abstract","Das Wirkspektrum von Flupirtin umfaßt analgetische, muskelentspannende und neuroprotektive Eigenschaften. Der Wirkmechanismus der Substanz war bislang unzureichend bekannt. In den letzten Jahren verdichteten sich jedoch Hinweise auf eine Interaktion von Flupirtin mit dem glutamatergen N-Methyl-D-Aspartat (NMDA)-Rezeptor. Obwohl eine direkte Wirkung am NMDA-Rezeptor nicht nachweisbar war. sprachen alle Befunde für eine indirekte Beeinflussung des NMDA-Rezeptors im Sinne eines funktionellen NMDA-Antagonismus. Es wurde somit postuliert, daß ein Wirkort ,,up- oder downstream\" vom NMDA-Rezeptor beeinflußt wird. Als solcher erwiesen sich die G-Protein gesteuerten einwärts gleichrichtenden K\"-Kanale (GIRK), deren Öffnung zu einer Stabilisierung des Ruhemembranpotentials neuronaler Zellen führt und dadurch eine indirekte Hemmung des NMDA-Rezeptors bewirkt. Flupirtin ist in therapeutisch relevanten Konzentrationen ein neuronaler K'-Kanalöffner (neuronal potassium Channel opener). Dieser Mechanismus vermag das Wirkspektrum von Flupirtin zu erklären. Damit erweist sich die selektive neuronale K+-Kanaloffnung (SNEPCO) als ein neues Wirkprinzip und Flupirtin als Prototyp einer neuen Substanzklasse mit analgetischen, muskelrelaxierenden und neuroprotektiven Eigenschaften. Die experimentellen Grundlagen dieser Arbeitshypothese und der daraus resultierenden Modellvorstellungen werden in einer vierstufigen Betrachtungsebene vorgestellt."],["dc.identifier.doi","10.1055/s-2007-994997"],["dc.identifier.gro","3151740"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8561"],["dc.language.iso","de"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0720-4299"],["dc.title","Neuronale Kaliumkanalöffnung durch Flupirtin"],["dc.title.subtitle","Opening of Neuronal K+ Channels by Flupirtine"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","857"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Journal of Neural Transmission"],["dc.bibliographiccitation.lastpage","867"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Kornhuber, J."],["dc.contributor.author","Bleich, S."],["dc.contributor.author","Wiltfang, J."],["dc.contributor.author","Maler, M."],["dc.contributor.author","Parsons, C. G."],["dc.date.accessioned","2017-09-07T11:44:33Z"],["dc.date.available","2017-09-07T11:44:33Z"],["dc.date.issued","2002"],["dc.description.abstract","The spectrum of action of flupirtine includes analgesia, muscle relaxation and neuroprotection. N-methyl-D-aspartate (NMDA) receptor antagonism has been discussed as a possible mechanism of action of this compound with little direct evidence. The objective of the present study was to develop a plausible model to explain flupirtine's spectrum of action. A four-stage strategy was selected for this purpose: Firstly, the serum concentration of flupirtine under therapeutic conditions was determined on the basis of the current literature. The second stage involved assessing the known in-vitro effects in light of the therapeutic active concentration. Using whole cell patch clamp recordings from cultured rat superior colliculus neurones interactions between flupirtine and NMDA receptors were assessed. Only very high concentrations of flupirtine antagonized inward currents to NMDA (200 μM) at −70 mV with an lC50 against steady-state responses of 182.1 ± 12.1 μM. The effects of flupirtine were voltage-independent and not associated with receptor desensitization making actions within the NMDA receptor channel or at the glycine modulatory site unlikely. NMDA receptor antagonism probably has little relevance for the clinical efficacy of flupirtine as the concentrations needed were far higher than those achieved in clinical practice. However, the activation of a G-protein-regulated inwardly rectifying K+ channel was identified as an interesting molecular target site of flupirtine. In the next stage, the central nervous spectrum of action of experimental K+ channel openers (PCO) was considered. As far as they have been studied, experimental K+ channel openers display a spectrum of action comparable to that of flupirtine. In the final stage, a global model was developed in which flupirtine stabilizes the resting membrane potential by activating inwardly rectifying K+ channels, thus indirectly inhibiting the activation of NMDA receptors. The model presented here reconciles the known functional NMDA receptor antagonism of flupirtine with the activation of K+ channels that occurs at therapeutic concentrations, thus providing an understanding of flupirtine's spectrum of action. This makes flupirtine the prototype of a clinically applicable substance group with analgesic, muscle-relaxant and neuroprotective properties."],["dc.identifier.doi","10.1007/s007020050206"],["dc.identifier.gro","3151702"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8521"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0300-9564"],["dc.title","Flupirtine shows functional NMDA receptor antagonism by enhancing Mg 2+ block via activation of voltage independent potassium channels"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","269"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","European Archives of Psychiatry and Clinical Neurosciences"],["dc.bibliographiccitation.lastpage","271"],["dc.bibliographiccitation.volume","251"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Schenk-Daprá, Bettina"],["dc.contributor.author","Stiens, Gerthild"],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Bandelow, Borwin"],["dc.contributor.author","Müller, Peter"],["dc.contributor.author","Niedmann, Paul Dieter"],["dc.contributor.author","Armstrong, Victor William"],["dc.contributor.author","Rüther, Eckart"],["dc.date.accessioned","2017-09-07T11:44:42Z"],["dc.date.available","2017-09-07T11:44:42Z"],["dc.date.issued","2006"],["dc.description.abstract","Objective The goal of this study was to identify adverse effects of the atypical neuroleptic clozapine on liver function and lipid metabolism. Methods Data which included serum levels of clozapine and its hepatic metabolite N-desmethyl clozapine were collected from medical records of patients treated with clozapine and controls. Results We identified a clozapine-associated marked elevation of plasma cholinesterase (ChE) with unchanged levels of AST, ALT or g-GT. ChE was correlated to the serum level of clozapine and even closer to N-desmethyl clozapine. For the total patient group we observed significant correlations of ChE with the body-mass index and body weight. However, clozapine-treated patients and controls did not differ with regard to body-mass index, triglycerides, and cholesterol. Conclusion We report for the first time a clozapine-associated and dose-dependent elevation of plasma ChE, which may be related to clozapine-associated effects on hepatic lipid metabolism or ChE enzyme induction."],["dc.identifier.doi","10.1007/pl00007544"],["dc.identifier.gro","3151720"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8541"],["dc.language.iso","en"],["dc.notes.status","public"],["dc.notes.submitter","chake"],["dc.relation.issn","0940-1334"],["dc.title","Clozapine-associated elevation of plasma cholinesterase"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","65"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Gerontology"],["dc.bibliographiccitation.lastpage","71"],["dc.bibliographiccitation.volume","47"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Hüther, Gerald"],["dc.contributor.author","Kornhuber, Johannes"],["dc.date.accessioned","2017-09-07T11:44:43Z"],["dc.date.available","2017-09-07T11:44:43Z"],["dc.date.issued","2001"],["dc.description.abstract","Over the past few years, molecular biological research has considerably deepened our understanding of the pathophysiological basis of Alzheimer’s dementia (AD). Although different genetic origins of the disease have been identified, all of the findings point to a common terminal sequence in familial AD. This consists of an increased production of β-amyloid peptides from β-amyloid precursor protein. For the cases of sporadic AD, which far outweigh the number of cases of familial AD, an impaired catabolism of the β-amyloid peptides may also be pathophysiologically decisive according to the latest findings. Research into the molecular level of AD makes it possible to identify points of attack for rational drug treatment of the disease, while molecular markers of AD are increasingly being used as a part of early and differential neurochemical diagnostics."],["dc.identifier.doi","10.1159/000052775"],["dc.identifier.gro","3151719"],["dc.identifier.pmid","11287729"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8539"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0304-324X"],["dc.title","Molecular Biology of Alzheimer’s Dementia and Its Clinical Relevance to Early Diagnosis and New Therapeutic Strategies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","72"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Pharmacopsychiatry"],["dc.bibliographiccitation.lastpage","74"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Scheschonka, A."],["dc.contributor.author","Bleich, S."],["dc.contributor.author","Buchwald, A. B."],["dc.contributor.author","Ruther, E."],["dc.contributor.author","Wiltfang, J."],["dc.date.accessioned","2017-09-07T11:44:38Z"],["dc.date.available","2017-09-07T11:44:38Z"],["dc.date.issued","2002"],["dc.description.abstract","In this report, we will describe the first case of obsessive-compulsive behaviour following oral corticosteroid treatment in a 75-year old adult male patient with pulmonal disease, but without previous psychiatric symptoms or organic brain disorder. We will also discuss the clinical and pathophysiological considerations."],["dc.identifier.doi","10.1055/s-2002-25022"],["dc.identifier.gro","3151718"],["dc.identifier.pmid","11951148"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8538"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0176-3679"],["dc.title","Development of Obsessive-Compulsive Behaviour Following Cortisone Treatment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","737"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of the American Geriatrics Society"],["dc.bibliographiccitation.lastpage","739"],["dc.bibliographiccitation.volume","57"],["dc.contributor.author","Alexopoulos, Panagiotis"],["dc.contributor.author","Günther, Florian"],["dc.contributor.author","Popp, Julius"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Wolf, Stefanie"],["dc.contributor.author","Kneib, Thomas"],["dc.contributor.author","Kurz, Alexander"],["dc.contributor.author","Richter-Schmidinger, Tanja"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Kornhuber, Johannes"],["dc.date.accessioned","2017-09-07T11:47:13Z"],["dc.date.available","2017-09-07T11:47:13Z"],["dc.date.issued","2009"],["dc.identifier.doi","10.1111/j.1532-5415.2009.02212.x"],["dc.identifier.gro","3149297"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5958"],["dc.notes.intern","Kneib Crossref Import"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","chake"],["dc.publisher","Wiley-Blackwell"],["dc.relation.issn","0002-8614"],["dc.title","PLASMA HOMOCYSTEINE AND CEREBROSPINAL FLUID NEURODEGENERATION BIOMARKERS IN MILD COGNITIVE IMPAIRMENT AND DEMENTIA"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Neuropsychopharmacology"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Maler, M."],["dc.contributor.author","Wiltfang, J."],["dc.contributor.author","Degner, Detlef"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Bleich, Stefan"],["dc.date.accessioned","2018-11-07T10:36:28Z"],["dc.date.available","2018-11-07T10:36:28Z"],["dc.date.issued","2003"],["dc.format.extent","S406"],["dc.identifier.doi","10.1016/S0924-977X(03)92244-9"],["dc.identifier.isi","000185412300650"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45333"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.conference","16th Congress of the European-College-of-Neuropsychopharmacology"],["dc.relation.eventlocation","PRAGUE, CZECH REPUBLIC"],["dc.relation.issn","0924-977X"],["dc.title","Homocysteine induces cell death of astrocytes in vitro"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","156"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Brain Research"],["dc.bibliographiccitation.lastpage","162"],["dc.bibliographiccitation.volume","1052"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Esselmann, Herrmann"],["dc.contributor.author","Wiltfang, J."],["dc.contributor.author","Kunz, N."],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Reulbach, Udo"],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Ruther, Eckart"],["dc.contributor.author","Kornhuber, Johannes"],["dc.date.accessioned","2018-11-07T10:56:49Z"],["dc.date.available","2018-11-07T10:56:49Z"],["dc.date.issued","2005"],["dc.description.abstract","The present study examined the effect of memantine, an uncompetitive NMDA receptor antagonist, on ethanol-induced NMDA receptor up-regulation. Primary glutamatergic rat hippocampal neurons were exposed to ethanol and memantine for 5 days. The ethanol-sensitive NMDA receptor subunits NR1, NR2A and NR213 were quantified by Western immunoblot analysis. Fxposure to ethanol (50 mM) caused an increase in the levels of NRI (137 +/- 11 % of untreated control, P = 0.009), NR2A (128 +/- 14 %. P 0.022) and N213 (136 +/- 119 %, P = 0.012). Coincubation with memantine (10 mu M) completely blocked the ethanol-induced up-regulation of NR1 (102, 4 %) NR2A (95 +/- 7 %) and NR2B (105 +/- 13 %). No effect of memantine on NR subunit expression was observable, except for NR2A, where a decrease (79 +/- 6 %, P = 0.034) was noted. Neither ethanol nor memantine alone or in combination were toxic in the concentrations tested. These results may provide a molecular explanation for beneficial effects of memantine on ethanol-induced glutamatergic hyperexcitability reflected in the ethanol withdrawal syndrome and on the development of ethanol dependence. (c) 2005 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.brainres.2005.06.017"],["dc.identifier.isi","000231493000005"],["dc.identifier.pmid","16009352"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50105"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0006-8993"],["dc.title","Mernantine inhibits ethanol-induced NMDA receptor up-regulation in rat hippocampal neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","599"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Clinical Pharmacokinetics"],["dc.bibliographiccitation.lastpage","612"],["dc.bibliographiccitation.volume","46"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Kennepohl, Evelin M."],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Kraus, Thomas"],["dc.contributor.author","Reulbach, Udo"],["dc.contributor.author","Meineke, Ingolf"],["dc.date.accessioned","2018-11-07T11:06:18Z"],["dc.date.available","2018-11-07T11:06:18Z"],["dc.date.issued","2007"],["dc.description.abstract","Background and objective: Memantine plasma concentrations show considerable interindividual. variability. High memantine plasma concentrations are associated with the occurrence of neuropsychiatric adverse effects such as confusion. The objective of the present study was, therefore, to investigate the reasons for the observed variability of the pharmacokinetics of memantine in a representative patient population and to explore patient covariates on drug disposition. Subjects: Fifty-six ambulatory Western European patients aged 50-91 years. Methods: This prospective study used a full population pharmacokinetic sampling design. After at least 11 days of continuous memantine intake, the patients provided pharmacokinetic profiles, with six measurements each over a 12-hour period, with a total of 335 serum memantine concentrations. Covariates considered for inclusion in the models were: subject demographic factors (age, total bodyweight, gender), laboratory tests (urinary pH), total daily dose of memantine, memantine formulation type, comedication eliminated via tubular secretion and smoking history. The model development was conducted in three sequential steps. First, an adequate basic structural model was chosen (e.g. a one-, two- or three-compartment pharmacokinetic model). The data were analysed to estimate population pharmacokinetic parameters with the nonlinear mixed-effects model computer program NONMEM. Second, the effects of covariates were investigated on post hoc estimates using multivariate statistics. Third, the covariates with significant effects in the second step were used to build a final covariate pharmacokinetic model, again using NONMEM. Results: A two-compartment model with first-order absorption satisfactorily described memantine pharmacokinetics. In the final regression model, total bodyweight, memantine formulation type (solution vs tablets) and concomitant medication eliminated via tubular secretion were all important determinants of the apparent clearance (CL/F). The final regression model was: CL/F (L/h) = (1.92 + 0.048 center dot BW (kg)) center dot 0.530(FRM) center dot 0.769(CMD) where FRM = 1 for patients receiving memantine solution, otherwise FRM = 0; CMD = 1 for patients receiving a comedication eliminated via tubular secretion, otherwise CMD = 0; and BW is bodyweight. Compared with the basic model, the final population pharmacokinetic model explained 61% of the interindividual variance of the apparent clearance. Conclusions: The population pharmacokinetic model that was developed identified a set of sources of variability in the apparent clearance of memantine, which can be used as a reference in order to optimise memantine therapy in Western European patients."],["dc.identifier.doi","10.2165/00003088-200746070-00005"],["dc.identifier.isi","000248182400005"],["dc.identifier.pmid","17596105"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/52272"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0312-5963"],["dc.title","Memantine pharmacotherapy - A naturalistic study using a population pharmacokinetic approach"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","56"],["dc.bibliographiccitation.issue","SH2"],["dc.bibliographiccitation.journal","Fortschritte der Neurologie · Psychiatrie"],["dc.bibliographiccitation.lastpage","61"],["dc.bibliographiccitation.volume","69"],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Bleich, K."],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Kornhuber, Johannes"],["dc.date.accessioned","2017-09-07T11:44:45Z"],["dc.date.available","2017-09-07T11:44:45Z"],["dc.date.issued","2002"],["dc.description.abstract","Glutamat ist der wichtigste erregende Neurotransmitter im zentralen Nervensystem. Es gibt Hinweise darauf, dass seine Aktivität bei schizophrenen Patienten vermindert, an anderen Stellen vermehrt ist. In den letzten Jahren wurden mit epidemiologischen, genetischen, histopathologischen und bildgebenden Untersuchungen deutliche Fortschritte in der Aufklärung der Krankheitsursachen erreicht und es wurden zunehmend integrative Modelle zur Pathogenese und Pathophysiologie schizophrener Psychosen entwickelt. Wenngleich auch verschiedene Vulnerabilitätsfaktoren und Stressoren zur Manifestation von schizophrenen Psychosen führen können, bildet die Glutamathypothese mit dem Modell eines kortiko-striato-thalamo-kortikalen Regelkreises weiterhin eine interessante Grundlage und bietet auch künftig zahlreiche Forschungsansätze, insbesondere in der weiteren Aufklärung der Affektion von Glutamatrezeptoren (z. B. NMDA-Rezeptoren), der glutamatergen Transmission sowie deren pharmakologische Beeinflussbarkeit. Glutamate is the most abundant amino acid in the brain, where it plays an important role as a well-established major excitatory neurotransmitter in the central nervous system. It has been suggested that reduced glutamate neurotransmission may be involved in the pathophysiology of schizophrenia. The glutamate hypothesis of schizophrenia postulates alterations in the glutamatergic system as an important neurobiochemical event in the pathophysiology of this group of psychotic disorders. An altered glutamate release from synaptosomes including a hypofunction of different glutamate receptors (i.e. NMDA receptors) from different brain areas have previously been reported. Furthermore, partial agonists at the glycine co-agonist site of the NMDA receptor might be a new approach in the treatment of schizophrenic symptoms but further studies are necessary to clarify the role and efficacy of these substances in schizophrenia. Changes in the glutamatergic cortico-striatal connections in schizophrenia could precipitate a potential perceptive overstimulation of the neocortex from thalamic input and an inhibiting influence of the striatum on the thalamus would modulate the information input of the cortex, thereby possibly counteracting the disturbed information processing which is relatively characteristic for schizophrenic psychoses."],["dc.identifier.doi","10.1055/s-2001-16531"],["dc.identifier.gro","3151738"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8559"],["dc.language.iso","de"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0720-4299"],["dc.title","Glutamaterge Neurotransmission bei Schizophrenien"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]