Repositioning Candidate Details
| Candidate ID: | R1219 |
| Source ID: | DB09089 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Trimebutine |
| Synonyms: | 2-Dimethylamino-2-phenylbutyl 3,4,5-trimethoxybenzoat; Trimebutine |
| Molecular Formula: | C22H29NO5 |
| SMILES: | CCC(COC(=O)C1=CC(OC)=C(OC)C(OC)=C1)(N(C)C)C1=CC=CC=C1 |
| Structure: |
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| DrugBank Description: | Trimebutine is a spasmolytic agent that regulates intestinal and colonic motility and relieves abdominal pain with antimuscarinic and weak mu opioid agonist effects. It is marketed for the treatment of irritable bowel syndrome (IBS) and lower gastrointestinal tract motility disorders, with IBS being one of the most common multifactorial GI disorders . It is used to restore normal bowel function and is commonly present in pharmaceutical mixtures as trimebutine maleate salt form. Trimebutine is not a FDA-approved drug, but it is available in Canada and several other international countries. |
| CAS Number: | 39133-31-8 |
| Molecular Weight: | 387.476 |
| DrugBank Indication: | Indicated for symptomatic treatment of irritable bowel syndrome (IBS) and treatment of postoperative paralytic ileus following abdominal surgery. |
| DrugBank Pharmacology: | Trimebutine is a spasmolytic agent that acts directly on smooth muscle to modulate gastric motility. It shows a "dual function" that stimulates or inhibits spontaneous contractions depending on the concentration and prior contractile activity in the preparation. Targeting ion conductance that regulates GI motility, trimebutine inhibits the inward calcium currents and calcium-dependent potassium currents in a concentration-dependent manner . At lower concentrations (1-10uM), trimebutine depolarizes the resting membrane potential without affecting the amplitude of contractions, which is thought to be mediated by inhibition of outward potassium currents. It is also shown to activate T-type Ca2+ channel and increase gastric emptying, intestinal and colonic contractility . At higher concentrations (100-300uM), reduced amplitude of spontaneous contractions and action potentials is thought to be mediated by inhibition of L-type Ca2+ channels and inward calcium current . Trimebutine mediates a local anesthetic action by acting as a weak agonist at mu opioid receptors. |
| DrugBank MoA: | At high concentrations, trimebutine is shown to inhibit the extracellular Ca2+ influx in the smooth muscle cells through voltage dependent L-type Ca2+ channels and further Ca2+ release from intracellular Ca2+ stores . Trimebutine is suggested to bind to the inactivated state of the calcium channel with high affinity. Reduced calcium influx attenuates membrane depolarization and decrease colon peristalsis. It also inhibits outward K+ currents in response to membrane depolarization of the GI smooth muscle cells at resting conditions through inhibition of delayed rectifier K+ channels and Ca2+ dependent K+ channels, which results in induced muscle contractions . Trimebutine binds to mu opioid receptors with more selectivity compared to delta or kappa opioid receptors but with lower affinity than their natural ligands. Its metabolites (N-monodesmethyl-trimebutine or nor-trimebutine), are also shown to bind to opoid receptors on brain membranes and myenteric synaptosomes . |
| Targets: | Mu-type opioid receptor agonist; Voltage-dependent L-type calcium channel inhibitor; Calcium-activated potassium channel inhibitor; Voltage-dependent T-type calcium channel activator; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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