New Pharmaceutical Approaches to the Treatment of IBS:Future Development & Research
R. Spiller, N. Coleman,
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