Tropisetron hydrochloride is a synthetic, potent and selective antagonist of 5-HT3A channel. In fluorescence polarization it was found to have an affinity 8.31 pKi (M) for 5-HT3A receptor. Tropisetron binds to an extracellular domain of the receptor. Tropisetron was found to have an analgesic and anti-inflammatory activity via inhibition of lipopolysaccharide (LPS) stimulated tumor necrosis factor (TNF) and interleukin-1-β release from human monocytes. This inhibition is conducted by preventing the phosphorylation of the p38 mitogen activated kinase (MAPK). Interestingly, when combined with acetaminophen in an experimental pain inducing assay, Tropisteron blocked the analgesic effect of acetaminophen thus indicating that perhaps the analgesic action of acetaminophen is also mediated through 5-HT receptors.
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