Investigational drugs targeting 5-HT6 receptors for the treatment of Alzheimer's disease.

Abstract

INTRODUCTION:

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.

AREAS COVERED:

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.

EXPERT OPINION:

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: Karsten Wicke, Andreas Haupt, Anton Bespalov
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 24 Issue 12 Pg. 1515-28 ( 2015) ISSN: 1744-7658 [Electronic] England
• PMID: 26548316 (Publication Type: Journal Article, Review)

Chemical References

• Drugs, Investigational
• Receptors, Serotonin
• Serotonin Antagonists
• serotonin 6 receptor

Topics

• Alzheimer Disease (drug therapy, physiopathology)
• Animals
• Cognition (drug effects)
• Drug Design
• Drugs, Investigational (pharmacology, therapeutic use)
• Humans
• Receptors, Serotonin (drug effects, metabolism)
• Serotonin Antagonists (pharmacology, therapeutic use)