5-HT6 receptor and cognition

Since its discovery in 1993 and subsequent development of selective antagonists, a growing number of studies support the use of serotonin 5-HT6 receptor antagonism as a promising mechanism for treating cognitive dysfunction. Lately, 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. There is even an antagonist, SB-742457, that has completed phase II trials for the treatment of Alzheimer's disease. In addition to describe preclinical and clinical evidence of the effect of 5-HT6 receptor compounds on cognition, this article will also focus on the purported biochemical and neurochemical mechanisms of action by which 5-HT6 receptor compounds could influence cognition in health and disease.

Research highlights► 5-HT6 receptor ligands are promising candidates for treating cognitive dysfunction. ► Several neurotransmitter systems mediate 5-HT6 receptor actions. ► 5-HT6 receptor antagonists have undergone clinical trials for the treatment of AD. ► Adenylate cyclase is not the only biochemical pathway associated to 5-HT6 receptors.