Irritable bowel syndrome (IBS) is a commonly diagnosed condition whose symptomatology is complex. Nevertheless, there is a growing desire to attempt to understand the pathophysiology of the associated visceral pain and gastrointestinal dysfunction.

Research efforts have focussed on the involvement of 5-hydroxytryptamine (5-HT; also known as serotonin or enteramine) as a possible chemical mediator. This stems from the fact that the majority of 5-HT in the body is synthesised and stored in gut enterochromaffin cells, from where it can be released in response to changes in pressure across the gut wall, as well as by noxious agents.

Of the multiplicity of 5-HT receptor types through which 5-HT mediates its actions, 5-HT3 and 5-HT4 receptors seem particularly important functionally in the gastrointestinal tract (see Sanger, 1996, Neurogastroenterol. Motil., 8(4): 319-31). Our own research effort has focussed predominantly on the
5-HT3 receptor, a 5-HT-gated cation channel, which is located exclusively on neurones where it can mediate rapid activation of nerve terminals and/or cell bodies. In the intestine, recent evidence suggests that 5-HT3 receptors occur not just on enteric nerves and sensory afferents but also on visceral nociceptive nerve terminals, and therefore 5-HT and 5-HT3 receptors might be implicated in the pain and disordered sensory perception of irritable bowel syndrome. Much of the evidence for a pivotal role for 5-HT3 receptors in this condition comes from studies with alosetron, which is a potent, selective and long-acting antagonist at this receptor.

The unique pharmacokinetic and pharmacodynamic profile of alosetron makes it an ideal drug with which to test the concept that a 5-HT3 receptor antagonist will provide benefit in the treatment of patients with IBS (see Humphrey et al., 1999, Aliment. Pharmacol. Ther., 13(suppl. 2): 31-38). Two large phase III clinical trials with alosetron have recently shown good efficacy in female sufferers of IBS with a diarrhoea-predominant bowel habit. Lotronex^TM (alosetron) may therefore be the first specific medicine for the treatment of patients with this common disease, currently poorly treated.