Otilonium: a potent blocker of neuronal nicotinic ACh receptors in bovine chromaffin cells

  title={Otilonium: a potent blocker of neuronal nicotinic ACh receptors in bovine chromaffin cells},
  author={Luis Gand{\'i}a and M{\'e}rcedes Villarroya and Baldomero Lara and Virginia Olmos and Juan A. Gilabert and M. G. L{\'o}pez and Rafael Mart{\'i}nez-Sierra and Ricardo Borges and A. G. Garcı́a},
  journal={British Journal of Pharmacology},
1 Otilonium, a clinically useful spasmolytic, behaves as a potent blocker of neuronal nicotinic acetylcholine receptors (AChR) as well as a mild wide‐spectrum Ca2+ channel blocker in bovine adrenal chromaffin cells. 2 45Ca2+ uptake into chromaffin cells stimulated with high K+ (70 mM, 1 min) was blocked by otilonium with an IC50 of 7.6 μm. The drug inhibited the 45Ca2+ uptake stimulated by the nicotinic AChR agonist, dimethylphenylpiperazinium (DMPP) with a 79 fold higher potency (IC50 = 0.096… 
Antimuscarinic, calcium channel blocker and tachykinin NK2 receptor antagonist actions of otilonium bromide in the circular muscle of guinea-pig colon
The present findings demonstrate that, in the µM range of concentrations, otilonium bromide acts as a muscarinic and tachykinin NK2 receptor antagonist and as a calcium channel blocker.
Acetylcholine nicotinic receptor subtypes in chromaffin cells
  • M. Criado
  • Biology, Chemistry
    Pflügers Archiv - European Journal of Physiology
  • 2017
In the adrenal gland, acetylcholine released on stimulation of the sympathetic splanchnic nerve activates neuronal-type nicotinic receptors (nAChRs) in chromaffin cells and triggers catecholamine secretion, which can act as agonists, antagonists or allosteric modulators.
Otilonium bromide | MedChemExpress
  • Biology
  • 2021
Octylonium bromide (SP63) is a spasmolytic agent that blocks L-Type Calcium channels in human colonic smooth muscle that reduces its predominant symptom (abdominal pain/ discomfort) more than placebo does.
Chromaffin Cells of the Adrenal Medulla: Physiology, Pharmacology, and Disease.
An updated account of well-established features of the molecular processes regulating CC function are provided, and a survey of the as-yet-unsolved but important questions relating to CC function and dysfunction are surveyed.
Otilonium Bromide: A Selective Spasmolytic for the Gastrointestinal Tract
  • S. Evangelista
  • Medicine
    The Journal of international medical research
  • 1999
Clinical studies have confirmed OB as a potent spasmolytic drug with a good tolerability profile and studies in patients with irritable bowel syndrome demonstrated OB to be superior to placebo and reference drugs in parameters such as pain, abdominal distension and motility.
Colonic smooth muscle cells and colonic motility patterns as a target for irritable bowel syndrome therapy: mechanisms of action of otilonium bromide
Otilonium bromide inhibits the main patterns of human sigmoid motility in vitro, which are spontaneous rhythmic phasic contractions, smooth muscle tone, contractions induced by stimulation of excitatory motor neurons and contraction induced by direct effect of excited neurotransmitters, thereby limiting excessive intestinal contractility and abdominal cramping.
Changes in nitrergic and tachykininergic pathways in rat proximal colon in response to chronic treatment with otilonium bromide
  • G. Cipriani, S. Gibbons, G. Farrugia
  • Medicine
    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
  • 2015
Otilonium bromide is used as a spasmolytic drug in the treatment of the functional bowel disorder irritable bowel syndrome but little is known about the effects of chronic administration of OB on enteric neurons, neuromuscular transmission, and interstitial cells of Cajal, key regulators of the gut function.
Oral bioavailability and enterohepatic recirculation of otilonium bromide in rats
A secondary peak was observed in the serum concentration-time profiles in non-BDC rats following both i.v. and oral administration, indicating that otilonium bromide was subject to enterohepatic recirculation.
Effect of otilonium bromide on contractile patterns in the human sigmoid colon
  • D. Gallego, M. Aulí, P. Clavé
  • Medicine
    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
  • 2010
The aim of this study was to characterize the pharmacological effects of OB on contractile patterns in the human sigmoid colon.


R56865 inhibits catecholamine release from bovine chromaffin cells by blocking calcium channels
The results are compatible with the idea that R56865 blocks Ca2+ entry into K+‐depolarized chromaffin cells by promoting the inactivation of voltage‐dependent Ca 2+ channels; this would lead to the limitation of the rise in [Ca2+]i and of the release of catecholamines.
It is concluded that tubocurarine acts selectively on the slow ionic channels, and hexamethonium acts on both fast and slow channels, the association rate constant being 2.8 × 106 m−1 s−1 at −80mV.
The channel‐blocking action of methonium compounds on rat submandibular ganglion cells
It is concluded that all of the effects of drugs of the polymethylene bis‐trimethylammonium (methonium) series on the characteristics of the synaptic currents recorded from voltage‐clamped rat submandibular ganglion cells have been studied and amplitude can be interpreted in terms of channel block.
Dotarizine versus flunarizine as calcium antagonists in chromaffin cells
The results suggest that dotarizine behaves as a Ca2+ antagonist in bovine chromaffin cells and exhibits a potency similar to flunarIZine in blocking Ca2- entry, Ca2+, channels, Cai2+ signals and secretion.
Octylonium bromide: a smooth muscle relaxant which interferes with calcium ions mobilization.
Interference with mobilization of cellular and extracellular Ca++ pools produced by different neurohormones is likely to be the mechanism responsible for octylonium bromide smooth muscle relaxant properties in both animals and humans.
α‐Bungarotoxin‐sensitive Nicotinic Receptors on Bovine Chromaffin Cells: Molecular Cloning, Functional Expression and Alternative Splicing of the α7 Subunit
Northern blot analysis showed that the α7 subunit, a main component of these α‐bungarotoxin‐sensitive acetylcholine receptors in avian and rat brain, is expressed in chromaffin cells, and cross‐linking and sucrose gradient experiments suggested that, like the muscular and neuronal acetyl choline receptors, this α7 receptor has a pentameric structure.
Pharmacological studies on otilonium bromide.
  • A. Giachetti
  • Biology, Medicine
    The Italian journal of gastroenterology
  • 1991
OB seems to exert its activity mainly on distal GI tract, and its spasmolytic effect may be due to its ability to inhibit Ca++ fluxes and to a direct action of the drug on the contractile proteins of the smooth muscle.
The level of intracellular Ca regulates many cellular processes, including neurotransmitter and hormone secretion, the activity of ion channels and enzymes, cytoskeletal function, cell proliferation,
Clinical and functional evaluation of the efficacy of otilonium bromide: a multicenter study in Italy.
It is concluded that, in irritable bowel syndrome (IBS) patients, OB is able to improve symptoms and to reduce stimulated motor activity of the sigmoid.