Disease relevance of Csag-144

• Mebeverine-induced perforated colon in distal intestinal syndrome of cystic fibrosis [1].
• Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients [2].
• During 12 weeks of treatment, alosetron was shown to elicit significant relief of abdominal pain and discomfort compared with placebo or mebeverine in female IBS patients with diarrhea [3].

Psychiatry related information on Csag-144

• Human motor activity in the small bowel is more reproducible than that in the large bowel; therefore the aim of this study was to determine in the small bowel the effects of oral mebeverine in both IBS patients and in healthy controls [4].

High impact information on Csag-144

• Overall, the system features are very favorable for applications such as drug impurity profiling as is illustrated by the analysis of mebeverine and related compounds (both charged and neutral) at the 0.25% (w/w) level [5].
• AIM: To compare the efficacy and tolerability of the new 5-HT3-receptor antagonist alosetron and the smooth muscle relaxant mebeverine in a double-blind, multicentre, randomized trial [2].
• Mebeverine did not significantly alter the gastric emptying rate of the intact capsule (2.9 (1.9-3.2) to 2.8 (2.6-4.0) h) however it induced a small but significant acceleration in small intestinal transit of the capsule (1.6 (0.8-2.0) h to 1.0 (0.52-1.32) h, P=0.02) [6].
• BACKGROUND AND AIM: Despite its widespread use in irritable bowel syndrome (IBS), limited clinical data exist on the effects of mebeverine hydrochloride on gastrointestinal motility [4].
• Also, after mebeverine the proportion of the migrating motor complex cycle occupied by phase 2 was reduced in IBS-D (P = 0.01), while phase 2 burst frequency was reduced in IBS-C (P < 0.05) [4].

Chemical compound and disease context of Csag-144

• CONCLUSION: According to this overview five drugs have proved their clinical efficacy in patients with irritable bowel syndrome, without significant adverse reactions: cimetropium bromide, pinaverium bromide, trimebutine, octilium bromide and mebeverine [7].
• The aim of the present study was to characterize the effect of mebeverine on both small intestinal motor activity and electrogenic epithelial transport in the urethane anesthetized ferret [8].
• Clinical data for up to 3 months of treatment indicate that alosetron is orally bioavailable in tablet form, is well tolerated and is significantly superior to both placebo and the smooth muscle relaxant, mebeverine, in improving perception of visceral pain, spasms and diarrhea in female diarrhea-predominant irritable bowel syndrome [9].
• A randomised, double-blind study of mebeverine versus dicyclomine in the treatment of functional abdominal pain in young adults [10].
• In conclusion, Mebeverine hydrochloride 200 mg b.i.d. (Colofac MR) was shown to be therapeutically equivalent to mebeverine hydrochloride 135 mg t.i.d. (Colofac) in the treatment of abdominal pain in IBS [11].

Biological context of Csag-144

• The results show that mebeverine undergoes rapid and extensive first-pass metabolism involving hydrolysis of the ester function, and that negligible circulating concentrations of the parent drug are found in humans [12].
• The hyperpolarization induced by a second addition of adrenaline to the preparation was decreased and sustained in the presence of mebeverine, while the decrease of the electrotonic potential evoked during the alpha 1 response was less pronounced [13].
• However, when administered i.v. but not i.j., the doses of mebeverine that inhibited jejunal motility also significantly reduced heart rate and arterial blood pressure [8].
• The amplitude and duration of the compound action potential evoked in the vagus nerve were decreased by mebeverine but not by the metabolites [14].
• In conclusion, the results confirm in vivo the antispasmodic effect of mebeverine and suggested that mebeverine can influence epithelial transport, probably in the direction of enhanced intestinal absorption [8].

Anatomical context of Csag-144

• Hyperpolarization and cessation of spike activity of the muscle cells, accompanied by an increased amplitude of the electrotonic potential were observed in the presence of mebeverine (6 X 10(-5] after block of the alpha 2-, beta- and muscarinic receptors [13].
• On the metabolism of the amphetamine-derived antispasmodic drug mebeverine: gas chromatography-mass spectrometry studies on rat liver microsomes and on human urine [15].
• Cisapride and mebeverine were more effective per given concentration, when delivered IL than IA in both the ileum and sigmoid colon preparations [16].

Associations of Csag-144 with other chemical compounds

• The HPLC methods for the determination of plasma concentrations of the antispasmodic agent mebeverine (0.01-10 micrograms/mL) and its hydrolysis product veratric acid (0.1-50 micrograms/mL) are presented [12].
• Using a background electrolyte containing 20 mM sodium dodecyl sulfate (SDS) and 10 mM sodium phosphate buffer, it is demonstrated that full MEKC runs of test mixtures of mebeverine and related compounds can be monitored by ESI-MS with satisfactory sensitivity [17].
• After intake of a single oral dose of 405 mg mebeverine hydrochloride in four healthy human volunteers, peak plasma concentrations of mebeverine acid were found to be 1000-fold higher than those of mebeverine alcohol, i.e. approximately 3 microg/ml versus 3 ng/ml [18].
• The transient hyperpolarization after mechanical stimulation was diminished after addition of mebeverine to the stimulation fluid when chloride transport was inhibited by bumetanide (BUME) but in the presence of amiloride (AMI), a sodium ion transport inhibitor, the drug did not influence the reaction [19].
• DESIGN: Double-blind, prospectively randomised, three-way crossover study of mebeverine, mefenamic acid and placebo during three consecutive menstrual cycles [20].

Gene context of Csag-144

• Mebeverine bound to beta 2- and alpha-receptors and inhibited phosphodiesterase activity and calcium accumulation [21].

Analytical, diagnostic and therapeutic context of Csag-144

• However, after oral administration of the same dose, only traces of mebeverine were found in plasma, with the exception of one rat [12].
• Development of a standardized analysis strategy for basic drugs using ion-pair extraction and high-performance liquid chromatography. VIII. Method construction for the determination of mebeverine in tablets and biological fluids [22].
• Evaluation of capillary supercritical fluid chromatography with mass spectrometric detection for the analysis of a drug (mebeverine) in a dog plasma matrix [23].
• Concomitant drug use and hospitalizations were increased in mebeverine users [24].
• The daily defaecation frequency was markedly decreased after treatment (pinaverlum bromide, 2.9+/-1.2 vs 2.0+/-1.0, P< 0.05; mebeverine, 2.7+/-1.1 vs 2.1+/-1.0, P< 0.05) [25].

References