Overview
- Thompson, A.J. et al. (2012) J. Pharmacol. Exp. Ther. 341, 350.
Alomone Labs VUF 10166 blocks 5-HT3A receptors expressed in HEK 293T cells.Currents were elicited by 10 µM 5-HT, delivered every 3 minutes. VUF 10166 (#V-115) was applied 30 seconds before stimulation at 1 ,10 and 100 nM, as indicated and inhibited the 5-HT induced current in a dose-dependent and reversible manner.
VUF 10166 is a potent and selective antagonist of 5-HT3A and B receptors. It binds specifically and with high affinity to 5-HT3A (IC50 ~ 0.04 nM) and blocks the serotonin binding site. There's evidence of lower affinity to 5-HT3A/B receptors due to the influence of an additional allosteric binding site in the heteromer2.
VUF 10166 is able to bind to an orthosteric binding site of HT3A and 5-HT3A/B receptors - A+A− and an A+B− interface. binding to the A+B− interface in the 5-HT3A/B receptor may decrease the affinity of ligands binding to the A+A− site by allosterically increasing the rate of ligand dissociation from the adjacent orthosteric site1,3.
The 5-HT3 receptor subtype is a member of the Cys-loop ligand-gated cation channels which are expressed throughout the central and peripheral nervous systems and mediates a variety of physiological functions4.
Competitive antagonists of 5-HT3 receptors are used to treat symptoms of emesis arising from chemotherapy treatment and postoperative emesis after anesthesia and surgery. There is also a limited use of antagonists for treating irritable bowel syndrome2.
