کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5829681 1558999 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeting glutamate system for novel antipsychotic approaches: Relevance for residual psychotic symptoms and treatment resistant schizophrenia
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Targeting glutamate system for novel antipsychotic approaches: Relevance for residual psychotic symptoms and treatment resistant schizophrenia
چکیده انگلیسی
Antipsychotics are the mainstay of schizophrenia treatment. However, approximately one third of schizophrenic patients do not respond or respond poorly to antipsychotics. Therefore, there is a need for new approaches that can improve schizophrenia treatment significantly. Promising strategies arise from the modulation of glutamatergic system, according to its proposed involvement in schizophrenia pathogenesis. In this review, we critically updated preclinical and clinical data on the modulation of glutamate N-methyl-D-aspartate (NMDA) receptor activity by NMDA-Rs co-agonists, glycine transporters inhibitors, AMPAkines, mGluR5 agonists, NMDA-Rs partial agonists. We focused on: 1) preclinical results in animal models mimicking the pathophysiology of psychosis, mainly believed to be responsible of negative and cognitive symptoms, and predicting antipsychotic-like activity of these compounds; and 2) clinical efficacy in open-label and double-blind trials. Albeit promising preclinical findings for virtually all compounds, clinical efficacy has not been confirmed for D-cycloserine. Contrasting evidence has been reported for glycine and D-serine, that may however have a role as add-on agents. More promising results in humans have been found for glycine transporter inhibitors. AMPAkines appear to be beneficial as pro-cognitive agents, while positive allosteric modulators of mGluR5 have not been tested in humans. Memantine has been proposed in early stages of schizophrenia, as it may counteract the effects of glutamate excitotoxicity correlated to high glutamate levels, slowing the progression of negative symptoms associated to more advanced stages of the illness.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 682, Issues 1–3, 5 May 2012, Pages 1-11
نویسندگان
, , , ,