Community hub
Recent from talks
Contribute something to knowledge base
Content stats: 0 posts, 0 articles, 1 media, 0 notes
Members stats: 0 subscribers, 0 contributors, 0 moderators, 0 supporters
Subscribers
Supporters
Contributors
Moderators
Trimebutine
Trimebutine is a drug with antimuscarinic and very weak mu opioid agonist effects. It is used for the treatment of irritable bowel syndrome and other gastrointestinal disorders. It is sometimes combined with simethicone as a combination drug. Trimebutine is formulated as a tablet or granules for oral suspension.
Trimebutine is a multimodal drug that acts on many receptors in the body. Its main effects are mediated through inhibition of voltage-gated L-type calcium channels, thereby decreasing calcium influx in smooth muscle in the gut. This mechanism explains its ability to slow peristalsis, which in turn helps with diarrhoea management in IBS patients. Antispasmodic effect is mediated through inhibition of inward rectifier potassium channels and calcium-dependend potassium channels. Moreover, trimebutine and its metabolite N-desmethyltrimebutine exert non-selective antagonistic effect on mAChRs, which is believed to potentiate its antispasmodic effects, as do many other drugs in this class.
Moreover, trimebutine and N-desmethyltrimebutine act as weak agonists of opioid receptors, specifically mu, delta and kappa receptor subtypes throughout the gut, which was shown in animal-model studies. Trimebutine exerts its effects in part due to causing a premature activation of phase III of the migrating motor complex in the digestive tract. This mode of action explains trimebutine's ability to mediate gastrointestinal motility in different parts of the gastrointestinal tract, both stimulating and inhibiting spontaneous contractions.
In vitro, trimebutine also exhibits antagonistic effects in sodium channels with IC50 equal 8.4 μM and inhibits glutamate release.
Oral bioavailability of trimebutine is nearly 100% for the maleate salt. Maximum serum concentration (Cmax) is achieved after 30 minutes for 100 mg dose and 0.88 h for 200 mg dose. The level of serum albumin binding is minimal. Half-life (t1/2) of 200 mg timebutine maleate is equal to 2.77 h.
Trimebutine exhibits first-pass metabolism effect, which in turn generates N-desmethyltrimebutine (nortrimebutine). Predominantly, trimebutine is excreted in urine, mainly as 2-dimethylamino-2-phenylbutan-1-ol, whereas fecal excretion is minimal (5-12%). Additionally, trimebutine might be metabolised through glucuronidation.
According to European Medicines Agency, formulations of trimebutine might be contaminated with N-nitrosamines. However, it was assigned CPCA Category 5 with acceptable daily intake of 1500 ng/day.
Trimebutine can increase the length of anaesthesia induced with d-tubocurarine. Other interactions include:
Trimebutine
Trimebutine is a drug with antimuscarinic and very weak mu opioid agonist effects. It is used for the treatment of irritable bowel syndrome and other gastrointestinal disorders. It is sometimes combined with simethicone as a combination drug. Trimebutine is formulated as a tablet or granules for oral suspension.
Trimebutine is a multimodal drug that acts on many receptors in the body. Its main effects are mediated through inhibition of voltage-gated L-type calcium channels, thereby decreasing calcium influx in smooth muscle in the gut. This mechanism explains its ability to slow peristalsis, which in turn helps with diarrhoea management in IBS patients. Antispasmodic effect is mediated through inhibition of inward rectifier potassium channels and calcium-dependend potassium channels. Moreover, trimebutine and its metabolite N-desmethyltrimebutine exert non-selective antagonistic effect on mAChRs, which is believed to potentiate its antispasmodic effects, as do many other drugs in this class.
Moreover, trimebutine and N-desmethyltrimebutine act as weak agonists of opioid receptors, specifically mu, delta and kappa receptor subtypes throughout the gut, which was shown in animal-model studies. Trimebutine exerts its effects in part due to causing a premature activation of phase III of the migrating motor complex in the digestive tract. This mode of action explains trimebutine's ability to mediate gastrointestinal motility in different parts of the gastrointestinal tract, both stimulating and inhibiting spontaneous contractions.
In vitro, trimebutine also exhibits antagonistic effects in sodium channels with IC50 equal 8.4 μM and inhibits glutamate release.
Oral bioavailability of trimebutine is nearly 100% for the maleate salt. Maximum serum concentration (Cmax) is achieved after 30 minutes for 100 mg dose and 0.88 h for 200 mg dose. The level of serum albumin binding is minimal. Half-life (t1/2) of 200 mg timebutine maleate is equal to 2.77 h.
Trimebutine exhibits first-pass metabolism effect, which in turn generates N-desmethyltrimebutine (nortrimebutine). Predominantly, trimebutine is excreted in urine, mainly as 2-dimethylamino-2-phenylbutan-1-ol, whereas fecal excretion is minimal (5-12%). Additionally, trimebutine might be metabolised through glucuronidation.
According to European Medicines Agency, formulations of trimebutine might be contaminated with N-nitrosamines. However, it was assigned CPCA Category 5 with acceptable daily intake of 1500 ng/day.
Trimebutine can increase the length of anaesthesia induced with d-tubocurarine. Other interactions include:
Recent media
Recent media