کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2494289 1115556 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Atypical antipsychotics as noncompetitive inhibitors of α4β2 and α7 neuronal nicotinic receptors
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Atypical antipsychotics as noncompetitive inhibitors of α4β2 and α7 neuronal nicotinic receptors
چکیده انگلیسی

It has been suggested that the interaction of antipsychotic medications with neuronal nicotinic receptors may increase the cognitive dysfunction associated with schizophrenia and may explain why current therapies only partially address this core feature of the illness. In the present studies we compared the effects of the atypical antipsychotics quetiapine, clozapine and N-desmethylclozapine to those of the typical antipsychotics haloperidol and chlorpromazine on the α4β2 and α7 nicotinic receptor subtypes. The binding of [3H]-nicotine to rat cortical α4β2 receptors and [3H]-methyllycaconitine to rat hippocampal α7 receptors was not affected by any of the compounds tested. However, Rb+ efflux evoked either by nicotine or the selective α4β2 agonist TC-1827 from α4β2 receptors expressed in SH-EP1 cells and nicotine-evoked [3H]-dopamine release from rat striatal synaptosomes were non-competitively inhibited by all of the antipsychotics. Similarly, α-bungarotoxin-sensitive epibatidine-evoked [3H]-norepinephrine release from rat hippocampal slices and acetylcholine-activated currents of α7 nicotinic receptors expressed in oocytes were inhibited by haloperidol, chlorpromazine, clozapine and N-desmethylclozapine. The inhibitory effects on nicotinic receptor function produced by the antipsychotics tested occurred at concentrations similar to plasma levels achieved in schizophrenia patients, suggesting that they may lead to clinically relevant effects on cognition.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 57, Issue 2, August 2009, Pages 183–191
نویسندگان
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