title: Investigational drugs targeting 5-HT6 receptors for the treatment of Alzheimer's disease.
abstract: BACKGROUND
  There are significant efforts invested into the discovery and development of novel treatments for Alzheimer's disease. While current discovery efforts and most scientific discussions seem to focus on disease-modifying therapy, there are several symptomatic therapy approaches that are being actively pursued. The goal of this review is to summarize the recent developments in the field of 5-HT6 receptor antagonists, a principle that has been extensively characterized preclinically and is now undergoing critical phases of clinical development.
  
  
  METHODS
  The article covers the current status of 5-HT6 receptor antagonists in clinical development. It also discusses the underlying mechanisms for the observed procognitive effects. The article is based on a search for investigational drugs using the key words '5-HT6', 'cognition', 'dementia', 'Alzheimer's disease', 'Phase II' and 'Phase III' in various databases and from conference abstracts.
  
  
  CONCLUSIONS
  After some period of little or no development activities, the field of 5-HT6 receptor antagonists attracted a lot of attention with three companies (GSK, Pfizer and Lundbeck) confirming aggressive development plans and initiating pivotal Phase II and III studies. These studies will be critical to prove that 5-HT6 receptor antagonists have a symptomatic efficacy profile that can be differentiated from that of currently used agents (cholinesterase inhibitors and the NMDA-antagonist memantine). Furthermore, there are several sets of data that point at a disease-modifying potential of this class of agents and these effects are likely to receive critical exploration if the ongoing symptomatic trials bring 5-HT6 antagonists closer to clinical use.
authors.affiliation: a AbbVie Deutschland GmbH & Co KG, Neuroscience Research , Department of Pharmacology , Knollstrasse , Ludwigshafen 67061 , Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Wicke
authors.affiliation: b AbbVie Deutschland GmbH & Co KG, Neuroscience Research , Department of Medicinal Chemistry , Knollstrasse , Ludwigshafen 67061 , Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Haupt
authors.affiliation: a AbbVie Deutschland GmbH & Co KG, Neuroscience Research , Department of Pharmacology , Knollstrasse , Ludwigshafen 67061 , Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Bespalov
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D003071:Cognition / Q000187:drug effects; D015195:Drug Design; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015507:Drugs, Investigational; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor
keywords: 5-HT6 receptor antagonists; Alzheimer’s disease; cognition; dementia