Chemical update on the potential for serotonin 5-HT6 and 5-HT7 receptor agents in the treatment of Alzheimer's disease

Bioorg Med Chem Lett. 2021 Oct 1:49:128275. doi: 10.1016/j.bmcl.2021.128275. Epub 2021 Jul 23.

Abstract

Despite the better understanding of the mechanisms underlying Alzheimer's Disease (AD) and launched clinical trials, no AD-modifying treatment based on a synthetic drug has been introduced for almost twenty years. The serotonin 5-HT6 and 5-HT7 receptors turned out to be promising biological targets for modulation of central nervous system dysfunctions including cognitive impairment. Within this paper, we evaluate the pharmacological potency of both, 5-HT6R and 5-HT7R, agents in search for novel AD treatment. An overview of chemical structures of the 5-HTRs ligands with simultaneous procognitive action which have undergone preclinical and clinical studies within the last 10 years has been performed.

Keywords: 5-HT(6)R antagonist; 5-HT(7)-antagonist; Alzheimer’s disease; Cognitive impairments; Procognitive activity; Serotonin receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Animals
  • Humans
  • Nootropic Agents / chemistry
  • Nootropic Agents / therapeutic use*
  • Receptors, Serotonin / metabolism*
  • Serotonin Antagonists / chemistry
  • Serotonin Antagonists / therapeutic use*
  • Serotonin Receptor Agonists / chemistry
  • Serotonin Receptor Agonists / therapeutic use*

Substances

  • Nootropic Agents
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • serotonin 6 receptor
  • serotonin 7 receptor