5-HT6 receptors and Alzheimer's disease

被引：86
作者：
Javier Ramirez, Maria [1 ,2 ]
机构：
[1] Univ Navarra, Ctr Appl Med Res CIMA, Dept Pharmacol, E-31080 Pamplona, Spain
[2] Univ Navarra, Ctr Appl Med Res CIMA, Dept Cellular & Mol Neuropharmacol, Div Neurosci, E-31080 Pamplona, Spain
来源：
ALZHEIMERS RESEARCH & THERAPY | 2013年 / 5卷 / 02期
关键词：
OBJECT RECOGNITION; COGNITIVE IMPAIRMENT; MESSENGER-RNA; SEROTONIN; LOCALIZATION; ANTAGONISTS; ACTIVATION; CLONING; MEMORY; INVOLVEMENT;
D O I：
10.1186/alzrt169
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
During the past 20 years, the 5-HT6 receptor has received increasing attention and become a promising target for improving cognition. Several studies with structurally different compounds have shown that not only antagonists but also 5-HT6 receptor agonists improve learning and memory in animal models. A large number of publications describing the development of ligands for this receptor have come to light, and it is now quite evident that 5-HT6 receptors have great pharmaceutical potential in terms of related patents. However, 5-HT6 receptor functionality is much more complex than initially defined. According to the existing data, different cellular pathways may be activated, depending on the drug being used. This article reviews preclinical and clinical evidence of the effects that 5-HT6 receptor compounds have on cognition. In addition, the biochemical and neurochemical mechanisms of action through which 5-HT6 receptor compounds can influence cognition will be described. Overall, several 5-HT6-targeted compounds can reasonably be regarded as powerful drug candidates for the treatment of Alzheimer's disease.
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页数：8
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共 54 条
[1]   Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats [J].
Arnt, Jorn ;
Bang-Andersen, Benny ;
Grayson, Ben ;
Bymaster, Franklin P. ;
Cohen, Michael P. ;
DeLapp, Neil W. ;
Giethlen, Bruno ;
Kreilgaard, Mads ;
McKinzie, David L. ;
Neill, Joanna C. ;
Nelson, David L. ;
Nielsen, Soren M. ;
Poulsen, Mette N. ;
Schaus, John M. ;
Witten, Louise M. .
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 2010, 13 (08) :1021-1033
[2]   5-HT6 receptor and cognition [J].
Codony, Xabier ;
Miguel Vela, Jose ;
Javier Ramirez, Maria .
CURRENT OPINION IN PHARMACOLOGY, 2011, 11 (01) :94-100
[3]   5-HT6 receptor blockade differentially affects scopolamine-induced deficits of working memory, recognition memory and aversive learning in mice [J].
Costa-Aze, Virginie Da Silva ;
Quiedeville, Anne ;
Boulouard, Michel ;
Dauphin, Francois .
PSYCHOPHARMACOLOGY, 2012, 222 (01) :99-115
[4]   The 5-HT6 receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus [J].
Dawson, LA ;
Nguyen, HQ ;
Li, P .
NEUROPSYCHOPHARMACOLOGY, 2001, 25 (05) :662-668
[5]   Two novel 5-HT6 receptor antagonists ameliorate scopolamine-induced memory deficits in the object recognition and object location tasks in Wistar rats [J].
de Bruin, N. M. W. J. ;
Prickaerts, J. ;
van Loevezijn, A. ;
Venhorst, J. ;
de Groote, L. ;
Houba, P. ;
Reneerkens, O. ;
Akkerman, S. ;
Kruse, C. G. .
NEUROBIOLOGY OF LEARNING AND MEMORY, 2011, 96 (02) :392-402
[6]   Acute onset by 5-HT6-receptor activation on rat brain brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein mRNA expression [J].
De Foubert, G. ;
O'Neill, M. J. ;
Zetterstrom, T. S. C. .
NEUROSCIENCE, 2007, 147 (03) :778-785
[7]   Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study [J].
Doody, Rachelle S. ;
Gavrilova, Svetlana I. ;
Sano, Mary ;
Thomas, Ronald G. ;
Aisen, Paul S. ;
Bachurin, Sergey O. ;
Seely, Lynn ;
Hung, David .
LANCET, 2008, 372 (9634) :207-215
[8]   Actions of novel agonists, antagonists and antipsychotic agents at recombinant rat 5-HT6 receptors:: A comparative study of coupling to Gαs [J].
Dupuis, Delphine S. ;
la Cour, Clotilde Mannoury ;
Chaput, Christine ;
Verriele, Laurence ;
Lavielle, Gilbert ;
Millan, Mark J. .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2008, 588 (2-3) :170-177
[9]   An update on the role of the 5-hydroxytryptamine6 receptor in cognitive function [J].
Fone, Kevin C. F. .
NEUROPHARMACOLOGY, 2008, 55 (06) :1015-1022
[10]   Neurochemical basis for symptomatic treatment of Alzheimer's disease [J].
Francis, Paul T. ;
Ramirez, Maria J. ;
Lai, Mitchell K. .
NEUROPHARMACOLOGY, 2010, 59 (4-5) :221-229
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