Disease relevance of diethyl-methyl-[2-[4-[(2-octoxybenzoyl)amino]benzoyl]oxyethyl]ammonium

• Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study [1].
• RESULTS: The reduction in the number of abdominal pain episodes was significantly higher (P < 0.01) in otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0%, vs. 30.2%; P < 0.05) [1].
• Safety data from clinical trials and postmarketing sources indicate that otilonium bromide is well tolerated, with a safety profile comparable to placebo in clinical trials and only two reported cases of adverse reactions (urticaria) among 10-year postmarketing data [2].
• Two spasmolytic drugs, N-butylscopolammonium bromide and octylonium bromide have been challenged against topical carbachol-induced contracture of gastric antrum, duodenum, jejunum, ileum, caecum, colon and rectum of the rat [3].

Psychiatry related information on diethyl-methyl-[2-[4-[(2-octoxybenzoyl)amino]benzoyl]oxyethyl]ammonium

• Notably the administration of otilonium bromide in rats receiving morphine together with naloxone decreased the intensity of certain withdrawal symptoms, such as excretion of faeces, wet dog shake behaviour, and elevated the nociceptive threshold values [4].
• Treatment of IBS patients with octylonium bromide (80 mg, qid, per os) for 5-7 days reduced their colonic response to eating to a very short increase in colonic motor activity limited to the first 30 min [5].
• CONCLUSION: These data suggest that otilonium bromide enhances sensory thresholds to recto-sigmoideal distention [6].
• In contrast to placebo, octylonium bromide significantly reduced pain and bloating, and significantly increased (p < 0.02) the pain threshold throughout the treatment period [7].
• Combining otilonium bromide with benzodiazepines, such as diazepam, may improve the efficacy of the agent with respect to GI symptoms, while also treating underlying anxiety disorders [2].

High impact information on diethyl-methyl-[2-[4-[(2-octoxybenzoyl)amino]benzoyl]oxyethyl]ammonium

• When excluding the low-quality trials, an improvement of global irritable bowel syndrome symptoms with all antispasmodics (OR: 2.1; 95% CI:1.8-2.9) was maintained only for octylonium bromide, but on the basis of only two studies [8].
• Otilonium bromide has been shown to interfere with the mobilization of calcium in intestinal smooth muscle, but the effects on other intestinal tissues have not been investigated [9].
• PAF receptor antagonists CV6209 and octylonium bromide abolished PAF-stimulated I(sc) [10].
• Otilonium bromide inhibits muscle contractions via L-type calcium channels in the rat colon [11].
• Radioactivity levels were very low in the plasma (ranging from 2.7 ng Eq/ml at 1.5 h to 0.6 ng Eq/ml at 24 h) as compared with those found in the gastrointestinal (GI) tract, indicating negligible systemic otilonium bromide absorption [12].

Biological context of diethyl-methyl-[2-[4-[(2-octoxybenzoyl)amino]benzoyl]oxyethyl]ammonium

• On the other hand, otilonium bromide produced a similar inhibitory effect on both membrane depolarization and contraction (IC50 38 microM and 45 microM, respectively) induced by the tachykinin NK2 receptor agonist [betaAla8]neurokinin A (4-10) [13].
• The aim of this study was to determine the plasma levels and the tissue distribution of otilonium bromide, measured as total radioactivity, after oral administration of 2 mg/kg of (14)C-labeled drug to rats [12].
• The clinical pharmacology of single doses of otilonium bromide in healthy volunteers [14].
• Colonic motility and gastric emptying in patients with irritable bowel syndrome. Effect of pretreatment with octylonium bromide [5].
• The interaction of Otilonium bromide (OB) with binding sites for 63 different receptors and ion channels in appropriate preparations has been investigated [15].

Anatomical context of diethyl-methyl-[2-[4-[(2-octoxybenzoyl)amino]benzoyl]oxyethyl]ammonium

• The radioactivity in large intestine walls was measurable at otilonium bromide concentrations in the range of micromole equivalents/kg, from 4 to 8 h after drug administration [12].
• We describe here the effects of otilonium bromide (an anticholinergic agent widely used as an intestinal spasmolytic) on whole-cell currents through Ca2+ channels (IBa) and catecholamine secretion in rat adrenal glands and isolated rat chromaffin cells [16].
• In radioligand binding experiments otilonium bromide produced a concentration-dependent inhibition of the binding of both an agonist ([125I]neurokinin A, Ki 7.2 microM) and an antagonist ([3H]SR 48968, Ki 2.2 microM) to membranes of Chinese hamster ovary cells transfected with the human tachykinin NK2 receptor [13].
• The competitive antagonism toward BaCl2-induced contraction of rat ileum and aorta suggested that octylonium bromide interferes with Ca++ mobilization [17].
• Sigmoid motility during distension was significantly reduced after octylonium bromide (p < 0.05), but it did not change after placebo [7].

Associations of diethyl-methyl-[2-[4-[(2-octoxybenzoyl)amino]benzoyl]oxyethyl]ammonium with other chemical compounds

• A rapid, simple, stability-indicating assay procedure for otilonium bromide, a smooth muscle relaxant agent, and diazepam in composite tablet analysis was developed with high-performance liquid chromatography [18].

Gene context of diethyl-methyl-[2-[4-[(2-octoxybenzoyl)amino]benzoyl]oxyethyl]ammonium

• Antimuscarinic, calcium channel blocker and tachykinin NK2 receptor antagonist actions of otilonium bromide in the circular muscle of guinea-pig colon [13].
• Otilonium bromide eliminated the APs superimposed on the depolarization induced by the tachykinin NK1 receptor agonist, [Sar9]substance P-sulphone and suppressed the corresponding contraction (IC50 43 microM) but had little effect on the sustained membrane depolarization induced by this agonist [13].

Analytical, diagnostic and therapeutic context of diethyl-methyl-[2-[4-[(2-octoxybenzoyl)amino]benzoyl]oxyethyl]ammonium

• The visual analogue scale of well-being revealed a significant improvement (P < 0.05) in patients taking otilonium bromide [1].
• The aim of this study is to evaluate in vitro the effect of otilonium bromide (OB) on the mechanical and electrical activities of the rat colonic smooth muscle using muscle bath, microelectrodes and patch-clamp techniques [11].
• These methods determine octylonium bromide in the presence of its degradation products in concentration ranges of 0.1-0.5 microgram/microL by densitometry and 4.5-22.5 micrograms/mL by colorimetry, with mean accuracies of 100.21 +/- 0.93 and 99.73 +/- 0.89%, respectively [19].
• Clinical and functional evaluation of the efficacy of otilonium bromide: a multicenter study in Italy [20].

References