Drug Information

Drug (ID: DG00276) and It's Reported Resistant Information

• Name: Trospium chloride
• Synonyms: Regurin; Sanctura
• Indication:
  In total 1 Indication(s)
  Discovery agent [ICD-11: N.A.]; Approved; [1]
• Formula: C25H30ClNO3
• IsoSMILES: C1CC[N+]2(C1)[C@@H]3CC[C@H]2CC(C3)OC(=O)C(C4=CC=CC=C4)(C5=CC=CC=C5)O.[Cl-]
• InChI: 1S/C25H30NO3.ClH/c27-24(25(28,19-9-3-1-4-10-19)20-11-5-2-6-12-20)29-23-17-21-13-14-22(18-23)26(21)15-7-8-16-26;/h1-6,9-12,21-23,28H,7-8,13-18H2;1H/q+1;/p-1/t21-,22+,23
• InChIKey: RVCSYOQWLPPAOA-DHWZJIOFSA-M
• PubChem CID: 5284631
• ChEBI ID: CHEBI:32270
• TTD Drug ID: D0U9FD
• VARIDT ID: DR01284
• DrugBank ID: DB00209

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-16: Genitourinary system diseases

Overactive bladder [ICD-11: GC50]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Overactive bladder [ICD-11: GC50.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Mdr1a/1b double knockout mice xenograft model; Mus musculus
• Experiment for Drug Resistance: [3H]trospium chloride tissue distribution assay
• Mechanism Description: P-gp-deficient mdr1a,b(-/-) knockout mice were given either 1 mg/kg trospium chloride orally or 1 mg/kg intravenously to analyze brain penetration, intestinal secretion, and hepatobiliary excretion of the drug. The concentrations of trospium chloride in the brain were up to 7 times higher in the mdr1a,b(-/-) knockout mice compared with wild-type mice (p < 0.05), making P-gp a limiting factor for the blood-brain barrier penetration of this drug. Moreover, the residence time of the drug in the central nervous system was significantly prolonged in mdr1a,b(-/-) knockout.

References

• Ref 1: The role of p-glycoprotein in limiting brain penetration of the peripherally acting anticholinergic overactive bladder drug trospium chloride. Drug Metab Dispos. 2009 Jul;37(7):1371-4. doi: 10.1124/dmd.109.027144. Epub 2009 Apr 23.