MDL 72222

Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter synthesized from the amino acid tryptophan by the enzyme tryptophan decarboxylase. The 5-HT3 channel is a ligand-gated ion channel receptor of the cys-loop channel family. It is a pentamer with five subunits surrounding a central channel¹.

MDL 72222 (Bemesetron) is a synthetic, potent and selective antagonist of the 5-HT3 receptor. MDL 72222 has an effective concentration of 1 nM - 1μM and an ED50 of 9.27 nM. MDL 72222 produces blockade of the Bezold-Jarisch effect of 5-HT in anaesthetized rats. Inhibition of the 5-HT receptor by MDL 72222 is selective since high doses of MDL 72222 fail to alter response to electrical stimulation of efferent vagus nerves. In contrast, MDL 72222 proves only a weak and essentially non-selective antagonist of responses mediated by the 5-HT M-receptor present on the cholinergic nerves of guinea-pig ileum. MDL 72222 does not block smooth muscle contractile responses elicited by oxytocin or mediated through 5-HT D-receptors². In addition, MDL 72222 also significantly reduces pancreatic enzyme secretion induced by luminal administration of L-trp or melatonin and reverses the effects of 5-HT on amylase secretion³.