Title:Otilonium Bromide: A Drug with a Complex Mechanism of Action
Volume: 24
Issue: 16
Author(s): Stefano Evangelista, Chiara Traini and Maria Giuliana Vannucchi*
Affiliation:
- Department of Experimental and Clinical Medicine, Research Unit of Histology and Embryology, University of Florence, Viale Pieraccini, 650139 Florence,Italy
Keywords:
Ca2+ channels, enteric neurons, gastrointestinal motility, Irritable Bowel Syndrome (IBS), muscarinic receptors, neurotransmission,
pain, tachykinins.
Abstract: Otilonium bromide (OB) is a drug with spasmolytic activity belonging to quaternary ammonium derivatives
and extensively used to treat patients affected by the Irritable Bowel Syndrome (IBS). Thanks to its
peculiar pharmacokinetic, OB concentrates in the large bowel wall and acts locally. From the pharmacodynamics
point of view, OB is able to inhibit i) the main patterns of human colonic motility in vitro; ii) the contractility
caused by excitatory motor neurons stimulation (pre-synaptic action) and iii) the contractility caused by the direct
action of excitatory neurotransmitters (post-synaptic action). Interestingly, these effects derive from a complex
interaction between the drug and several cellular targets. The main action consists in the blockade of Ca2+ entry
through L-type Ca2+ channels and interference with intracytoplasmatic Ca2+ mobilization necessary for SMC
contraction, thus preventing excessive bowel contractions and abdominal cramps. Further, OB blocks the T-type
Ca2+ channels and interferes with the muscarinic responses; it interacts, directly or indirectly, with the tachykinin
receptors on SMC and on primary afferent neurons whose combined effects may result in the reduction of motility
and abdominal pain. In summary, a revision of this complex picture of OB activity could help to better address
its therapeutic use.
