New Pharmaceutical Approaches to the Treatment of IBS:Future Development & Research

Authors N. Coleman, R. Spiller.


Current approaches to treatment of Irritable Bowel Syndrome
(IBS) aim to normalise disturbed intestinal physiology.
The most effective centrally acting drugs are tricyclic
antidepressants. Alosetron, a 5-HT3 receptor antagonist
is effective in women with diarrhea-predominant IBS
whilst tegaserod and prucalopride are 5-HT4 agonists enhancing
bowel motility in constipation-predominant IBS.
Serotonergic receptor modulation has been the first targeted
pharmacological intervention. The development of new
drugs constitutes a major challenge as there are many targets
along the brain-gut axis and the enteric nervous system
(ENS). Newer tricyclic antidepressants with fewer side
effects and corticotrophin releasing factor-1 (CRF-1) antagonists
are examples of future centrally acting drugs.
Agents that alter visceral sensitivity include kappa-opioid
agonists (fedotozine, trimebutine, asimadoline), alpha-2
adrenoreceptor agonists (clonidine, lidamidine), tachykinin
receptor antagonists (neurokinin A, substance P) and
other experimental anti-nociceptive drugs (GABA-B receptor
agonists). COX-2 inhibitors may be effective for postinfectious
IBS. Drugs potentially useful in controlling intestinal
motility and secretion other than serotonergic receptors
modulators, include muscarinic receptors antagonists
(derifenacin, zamenifenacin), octreotide and CCK-1
receptor antagonists (dexloglumide). Neurotrophins (NT-
3 and brain derived neurotrophic factor) are promising factors
for the treatment of IBS patients with constipation. The development of new and effective drugs for IBS requires
a more detailed understanding of pathophysiologic mechanisms,
a fact that will allow us a more targeted intervention.
Key words: Irritable bavel syndrome, visceral sensitivity tricyclic
antidepressants, muscarinic receptors
Special Topics