Details of the Drug Combination

General Information of Drug Combination (ID: DCE81VD)

• Drug Combination Name: Tamsulosin + Tolterodine
• Indication: Prostatitis; Status: Phase 1 [1]
• Component Drugs:
  Tamsulosin (DM5QF9V): Small molecular drug
  Tolterodine (DMSHPW8): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tamsulosin

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[2]
Urinary retention	MF50.3	Approved	[3]

Tamsulosin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor alpha-1A (ADRA1A)	TTNGILX	ADA1A_HUMAN	Modulator	[6]

Tamsulosin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[7]

Tamsulosin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Affects Binding	[8]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[9]

Indication(s) of Tolterodine

Disease Entry	ICD 11	Status	REF
Overactive bladder	GC50.0	Approved	[4]
Priapism	N.A.	Investigative	[5]

Tolterodine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Muscarinic acetylcholine receptor M3 (CHRM3)	TTQ13Z5	ACM3_HUMAN	Antagonist	[10]

Tolterodine Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[12]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[11]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[11]

References

• [1] ClinicalTrials.gov (NCT00913315) Efficacy Study of Tamsulosin and Tolterodine Treatment for Chronic Prostatitis
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 488).
• [3] Tamsulosin FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Tolterodine FDA Label
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Identification of cytochrome P450 isozymes involved in metabolism of the alpha1-adrenoceptor blocker tamsulosin in human liver microsomes. Xenobiotica. 1998 Oct;28(10):909-22.
• [8] Cell membrane chromatography competitive binding analysis for characterization of 1A adrenoreceptor binding interactions. Anal Bioanal Chem. 2011 Jul;400(10):3625-33. doi: 10.1007/s00216-011-5026-z. Epub 2011 May 5.
• [9] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [10] Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004 Jun;309(3):1148-53.
• [11] Tolterodine, a new muscarinic receptor antagonist, is metabolized by cytochromes P450 2D6 and 3A in human liver microsomes. Drug Metab Dispos. 1998 Apr;26(4):289-93.
• [12] Effect of the CYP2D6*10 genotype on tolterodine pharmacokinetics. Drug Metab Dispos. 2010 Sep;38(9):1456-63.