Serotonergic modulating drugs for functional gastrointestinal diseases

After many years of basic research we have now begun to learn how to manipulate the serotonergic mechanisms within the gut. This has lead to a number of significant advances including 5HT(3) antagonists for the treatment of functional diarrhoea, 5HT(4) agonists for the treatment of constipation and 5HT(1) agonists for the treatment of impaired fundal relaxation. Initial enthusiasm has been somewhat dented by the withdrawal of alosetron because of ischaemic colitis, but it remains to be seen whether this adverse event will be seen with other 5HT(3) antagonists. Finally it should be recognized that, in a substantial proportion of patients attending clinics complaining of functional symptoms, anxiety is a major component. The drugs so far described are by and large devoid of CNS effects. It remains possible therefore that a drug which combines both peripheral and central effects would likely to be beneficial.