Abstract
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.
Highlights
Alzheimer’s disease (AD), the most common cause of dementia among older people, is characterized by behavioral disorders and a progressive decline in memory function
Extensive serotonergic denervation has been described in AD, it is not yet fully understood whether these changes are a cause or a consequence of the neurodegeneration in the illness [1]
A combined treatment of SB-271046 with an acetylcholinesterase inhibitor produced an additive increase in passive avoidance and significantly reversed scopolamine-induced amnesic effects [41]. This combined administration of subthreshold doses of two novel selective 5-HT6 antagonists, compounds CMP X and CMP Y, with the acetylcholinesterase inhibitor donepezil (Aricept®; Eisai, Tokyo, Japan) enhanced memory performance in young Wistar rats with cognitive deficits induced by scopolamine [40]
Summary
Alzheimer’s disease (AD), the most common cause of dementia among older people, is characterized by behavioral disorders and a progressive decline in memory function. One of the more consistent findings regarding the involvement of 5-HT6 receptors in memory is the ability of the 5-HT6 receptor antagonist to reverse a scopolamine-induced cognitive deficit in the Morris water maze or novel object recognition test [40] This finding would be in line with the hypothesis that 5-HT6 receptor functions are mediated, at least partially, by a modulation of the cholinergic neurotransmission. A combined treatment of SB-271046 with an acetylcholinesterase inhibitor produced an additive increase in passive avoidance and significantly reversed scopolamine-induced amnesic effects [41] This combined administration of subthreshold doses of two novel selective 5-HT6 antagonists, compounds CMP X and CMP Y, with the acetylcholinesterase inhibitor donepezil (Aricept®; Eisai, Tokyo, Japan) (approved for symptomatic treatment of AD) enhanced memory performance in young Wistar rats with cognitive deficits induced by scopolamine [40]. Competing interests The author declares that she has no competing interests
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
