Allosteric modulation of the 5-HT3 receptor

5-Hydroxytryptamine type 3 (5-HT3) receptors are ligand-gated ion channels that play important roles in depression, anxiety, substance abuse, emesis, inflammatory pain, spinal nociception, gastrointestinal function, and cardiovascular reflexes. Probably the most studied modulators of 5-HT3 receptors are the high affinity competitive ‘setron’ antagonists typified by ondansetron. However, there exists a broad range of compounds that modulate the 5-HT3 receptor, not through the orthosteric site but by binding to allosteric sites. Most notable are therapeutic compounds ascribed to certain targets but that allosterically modulate 5-HT3 receptors at clinically relevant concentrations.

Research highlights
► Some clinically relevant compounds are allosteric modulators of 5-HT3 receptors.
► Subunit compositions of receptors influence effects of allosteric modulators.
► Heteromeric receptors contain an increased number of potential allosteric sites.