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Details

Stereochemistry ACHIRAL
Molecular Formula C29H43N2O4
Molecular Weight 483.6627
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 1

SHOW SMILES / InChI
Structure of OTILONIUM

SMILES

CCCCCCCCOC1=CC=CC=C1C(=O)NC2=CC=C(C=C2)C(=O)OCC[N+](C)(CC)CC

InChI

InChIKey=NQHNLNLJPDMBFN-UHFFFAOYSA-O
InChI=1S/C29H42N2O4/c1-5-8-9-10-11-14-22-34-27-16-13-12-15-26(27)28(32)30-25-19-17-24(18-20-25)29(33)35-23-21-31(4,6-2)7-3/h12-13,15-20H,5-11,14,21-23H2,1-4H3/p+1

HIDE SMILES / InChI

Molecular Formula C29H43N2O4
Molecular Weight 483.6627
Charge 1
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.drugs.com/international/otilonium-bromide.html | https://www.ncbi.nlm.nih.gov/pubmed/8867109 | https://www.ncbi.nlm.nih.gov/pubmed/25057296

Otilonium is a musculotropic spasmolytic agent belonging to the family of quaternary ammonium derivatives and successfully used in the treatment of patients affected by Irritable bowel syndrome (IBS) due to its specific pharmacokinetic and pharmacodynamic properties. The positive polarity of the head of the Otilonium molecule determines the main pharmacokinetic property of this drug: a minimal systemic absorption and the consequently high safety profile. Studies on animal models revealed a specific Otilonium accumulation in colonic circular muscle at therapeutic µm concentrations, while its plasma levels were 1000 times lower, together with a poor penetration of the drug in the central nervous system. Consistently, after oral administration to healthy volunteers, the Otilonium plasmatic concentration was very low, less than 1% of the drug was eliminated by urine, and 97% was eliminated by feces. Recent clinical studies showed comparable safety and tolerability for Otilonium and placebo. Otilonium was shown to inhibit the main patterns of human sigmoid motility in vitro, including: the tone of smooth muscle cells (SMCs); the rhythmic phasic contractions induced by the interstitial cells of Cajal; and the strong contractions induced by stimulation of enteric motor neurons mainly by blocking the calcium influx through L-type calcium channels on SMCs. Recent in vitro studies using cultured human colonic SMCs to further assess the musculotropic spasmolytic properties of Otilonium confirmed that this drug causes smooth muscle relaxation through the inhibition of voltage-gated calcium channels (L-type > T-type) and the inhibition of muscarinic and tachykinergic effects.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Obimal

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Otilonium bromide enhances sensory thresholds of volume and pressure in patients with irritable bowel syndrome.
2001 Jan-Dec
Optimisation and validation of a capillary electrophoresis method for the simultaneous determination of diazepam and otilonium bromide.
2001 Oct
Extended analysis of a double-blind, placebo-controlled, 15-week study with otilonium bromide in irritable bowel syndrome.
2002 Dec
The colon-selective spasmolytic otilonium bromide inhibits muscarinic M(3) receptor-coupled calcium signals in isolated human colonic crypts.
2002 Dec
Multicenter phase III clinical trial of otilonium bromide in irritable bowel syndrome.
2002 Mar-Apr
Quaternary ammonium derivatives as spasmolytics for irritable bowel syndrome.
2004
Otilonium bromide inhibits muscle contractions via L-type calcium channels in the rat colon.
2004 Apr
Suppressive activity of tiotropium bromide on matrix metalloproteinase production from lung fibroblasts in vitro.
2008
Oral bioavailability and enterohepatic recirculation of otilonium bromide in rats.
2008 Jan
Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis.
2008 Nov 13
Increased paracellular absorption by bile salts and P-glycoprotein stimulated efflux of otilonium bromide in Caco-2 cells monolayers as a model of intestinal barrier.
2008 Sep
Effect of otilonium bromide on contractile patterns in the human sigmoid colon.
2010 Jun
T-type Ca(2+) channel modulation by otilonium bromide.
2010 May
Determination of the unstable drug otilonium bromide in human plasma by LC-ESI-MS and its application to a pharmacokinetic study.
2010 Oct 15
Tiotropium bromide inhibits TGF-β-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro.
2010 Sep 7
Patents

Patents

Sample Use Guides

3 tablets (3 × 40 mg) daily before meals (120 mg Otilonium/day)
Route of Administration: Oral
Human circular smooth muscle cells were used for activity evaluation. To determine the effect of Otilonium on ionic conductances in human jejunal circular smooth muscle, we patch clamped enzymatically dissociated cells with Cs+ in the pipette to block outward K+ currents and with NaCl or NMDG-Cl Ringer’s extracellular solution. Electrodes were coated with R6101 (Dow Corning, Midland, MI, USA) and fire polished to a final resistance of 3–5 M. Currents were amplified, digitized and processed using an Axopatch 200B amplifier, a Digidata 1200, and pCLAMP 8 software (Axon Instruments, Foster City, CA, USA). In experiments examining Na+ or Ca2+ current, whole cell records were sampled at 10 kHz and filtered at 4 kHz with an eight-pole Bessel filter. For these experiments, cells were held at -100 mV and pulsed from -80 to +35 mV in 5 mV intervals for 50 ms. Otilonium (0.09–9 mkM) was used as this reproduced clinical intracellular concentrations. In human circular smooth muscle cells, Otilonium inhibited L-type Ca2+ current by 25% at 0.9 mkM and 90% at 9 mkM.
Substance Class Chemical
Created
by admin
on Sat Dec 16 05:54:50 GMT 2023
Edited
by admin
on Sat Dec 16 05:54:50 GMT 2023
Record UNII
6330179ARU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OTILONIUM
WHO-DD  
Common Name English
Otilonium [WHO-DD]
Common Name English
ETHANAMINIUM, N,N-DIETHYL-N-METHYL-2-((4-((2-(OCTYLOXY)BENZOYL)AMINO)BENZOYL)OXY)-
Systematic Name English
OTILONIUM CATION
Common Name English
N,N-DIETHYL-N-METHYL-2-(4-(2-(OCTYLOXY)BENZAMIDO)BENZOYLOXY)ETHANAMINIUM
Systematic Name English
OCTYLONIUM
Common Name English
OTILONIUM ION
Common Name English
Code System Code Type Description
SMS_ID
100000085485
Created by admin on Sat Dec 16 05:54:50 GMT 2023 , Edited by admin on Sat Dec 16 05:54:50 GMT 2023
PRIMARY
EPA CompTox
DTXSID0048391
Created by admin on Sat Dec 16 05:54:50 GMT 2023 , Edited by admin on Sat Dec 16 05:54:50 GMT 2023
PRIMARY
EVMPD
SUB03554MIG
Created by admin on Sat Dec 16 05:54:50 GMT 2023 , Edited by admin on Sat Dec 16 05:54:50 GMT 2023
PRIMARY
PUBCHEM
72093
Created by admin on Sat Dec 16 05:54:50 GMT 2023 , Edited by admin on Sat Dec 16 05:54:50 GMT 2023
PRIMARY
DRUG BANK
DB13500
Created by admin on Sat Dec 16 05:54:50 GMT 2023 , Edited by admin on Sat Dec 16 05:54:50 GMT 2023
PRIMARY
CAS
105360-89-2
Created by admin on Sat Dec 16 05:54:50 GMT 2023 , Edited by admin on Sat Dec 16 05:54:50 GMT 2023
PRIMARY
RXCUI
32311
Created by admin on Sat Dec 16 05:54:50 GMT 2023 , Edited by admin on Sat Dec 16 05:54:50 GMT 2023
PRIMARY
FDA UNII
6330179ARU
Created by admin on Sat Dec 16 05:54:50 GMT 2023 , Edited by admin on Sat Dec 16 05:54:50 GMT 2023
PRIMARY
KEGG
32311
Created by admin on Sat Dec 16 05:54:50 GMT 2023 , Edited by admin on Sat Dec 16 05:54:50 GMT 2023
PRIMARY
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