Since its discovery in 1993 and subsequent development of selective antagonists, a growing number of studies support the use of serotonin 5-HT(6) 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-HT(6) 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-HT(6) receptor compounds on cognition, this article will also focus on the purported biochemical and neurochemical mechanisms of action by which 5-HT(6) receptor compounds could influence cognition in health and disease.
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