Natural Negative Allosteric Modulators of 5-HT₃ Receptors

Molecules. 2018 Dec 3;23(12):3186. doi: 10.3390/molecules23123186.

Abstract

Chemotherapy-induced nausea and vomiting (CINV) remain the most common and devastating side-effects associated with cancer chemotherapy. In recent decades, several lines of research emphasize the importance of 5-hydroxytryptamine3 (5-HT3; serotonin) receptors in the pathogenesis and treatment of CINV. 5-HT₃ receptors are members of ligand-gated ion channels that mediate the rapid and transient membrane-depolarizing effect of 5-HT in the central and peripheral nervous system. These receptors play important roles in nausea and vomiting, as well as regulation of peristalsis and pain transmission. The development of antagonists for 5-HT₃ receptor dramatically improved the treatment of CINV in cancer patients. In fact, the most common use of 5-HT₃ receptor antagonists to date is the treatment of nausea and vomiting. In recent years, there has been an increasing tendency to use natural plant products as important therapeutic entities in the treatment of various diseases. In this article, we examined the results of earlier studies on the actions of natural compounds on the functional properties of 5-HT₃ receptors. It is likely that these natural modulators of 5-HT₃ receptors can be employed as lead structures for the synthesis of therapeutic agents for treating CINV in future clinical studies.

Keywords: 5-hydroxytryptamine3 receptor antagonists; 5-hydroxytryptamine3 receptors; chemotherapy-induced nausea and vomiting; negative allosteric modulators.

Publication types

  • Review

MeSH terms

  • Allosteric Regulation
  • Antineoplastic Agents / adverse effects
  • Binding Sites
  • Cannabidiol / pharmacology
  • Humans
  • Nausea / chemically induced
  • Nausea / metabolism*
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Serotonin 5-HT3 Receptor Antagonists / chemistry
  • Serotonin 5-HT3 Receptor Antagonists / pharmacology*
  • Terpenes / pharmacology
  • Vomiting / chemically induced
  • Vomiting / metabolism*
  • Zingiber officinale / chemistry

Substances

  • Antineoplastic Agents
  • Receptors, Serotonin, 5-HT3
  • Serotonin 5-HT3 Receptor Antagonists
  • Terpenes
  • Cannabidiol