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Pharmacotherapy: non-serotonergic mechanisms

Correspondence to:
Correspondence to:
Professor R Spiller, Division of Gastroenterology, University Hospital, Nottingham NG7 2UH, UK;
robin.spiller{at}nottingham.ac.uk

ABSTRACT
Antidepressants rapidly relieve pain in irritable bowel syndrome (IBS) and are effective at low doses. Noradrenaline reuptake inhibitors appear to be more effective than selective serotonergic reuptake inhibitors, suggesting that pathways other than those modulated by serotonin may be involved in visceral sensation. Visceral sensitivity is reduced by both centrally and peripherally acting opioids, suggesting the possible existence of an endogenous opioid deficiency in patients with IBS. The ₂ adrenoceptor antagonist clonidine, as well as somatostatin, oxytocin, and possibly amitriptyline have also been shown to act as visceral analgesics. As knowledge increases, there are undoubtedly many other possible targets, and new drugs currently undergoing development may provide future benefit in patients with IBS.

Keywords: irritable bowel syndrome; tricyclic antidepressants; ₂ adrenoceptor agonists; opioids; somatostatin; selective serotonin reuptake inhibitors

Abbreviations: CCK, cholecystokinin; CNS, central nervous system; DNIC, descending nociceptive inhibitory control; IBS, irritable bowel syndrome; NK1, neurokinin; SSRIs, selective serotonergic reuptake inhibitors; 5-HT, serotonin