Details of the Drug Combination

General Information of Drug Combination (ID: DCZMEHT)

• Drug Combination Name: Dextromethorphan + Tindamax
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Dextromethorphan (DMUDJZM): Small molecular drug
  Tindamax (DM3OWT4): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 9.64
  Bliss Independence Score: 9.64
  Loewe Additivity Score: 23.55
  LHighest Single Agent (HSA) Score: 23.57

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Dextromethorphan

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[2]
Common cold	CA00	Approved	[2]
Cough	MD12	Approved	[3]
Fever	MG26	Approved	[2]
Headache	8A80-8A84	Approved	[2]
Rhinitis	FA20	Approved	[2]
Vasomotor/allergic rhinitis	CA08	Approved	[2]

Dextromethorphan Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor sigma 1 (OPRS1)	TT5TPI6	SGMR1_HUMAN	Agonist	[9]

Dextromethorphan Interacts with 10 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[11]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[12]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[13]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[14]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[15]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[14]
Cholesterol 24-hydroxylase (CYP46A1)	DEKP5HX	CP46A_HUMAN	Metabolism	[16]
Cytochrome P450 102A1 (cyp102)	DE4OGUF	CPXB_BACMB	Metabolism	[17]
Cytochrome P450 130A1 (cyp130)	DE6CQ0I	CP130_MYCTU	Metabolism	[18]

Dextromethorphan Interacts with 12 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Methylation	[19]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Decreases Methylation	[19]
Cholesterol 24-hydroxylase (CYP46A1)	OTJ27FOX	CP46A_HUMAN	Decreases Methylation	[16]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases Response To Substance	[20]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Secretion	[21]
Beta-hexosaminidase subunit beta (HEXB)	OTROYLCR	HEXB_HUMAN	Increases Secretion	[21]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Secretion	[21]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[21]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[22]
Mas-related G-protein coupled receptor member X2 (MRGPRX2)	OT2XA799	MRGX2_HUMAN	Affects Binding	[21]
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Affects Metabolism	[8]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Affects Metabolism	[8]

Indication(s) of Tindamax

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[4]
Bacterial vaginosis	MF3A	Approved	[5]
Trichomoniasis	N.A.	Approved	[6]
Giardiasis	N.A.	Investigative	[7]

Tindamax Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[23]
Nitroreductase (NTR)	DEAN5EW	NFSB_ENTCL	Metabolism	[24]

Tindamax Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[25]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Dextromethorphan FDA Label
• [3] 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: 6953).
• [4] 2004 approvals: the demise of the blockbuster. Nat Rev Drug Discov. 2005 Feb;4(2):93-4.
• [5] Tinidazole. 2021 Mar 17. Drugs and Lactation Database (LactMed?) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006C.
• [6] Tinidazole (Tindamax)--a new option for treatment of bacterial vaginosis. Med Lett Drugs Ther. 2007 Sep 10;49(1269):73-4.
• [7] Tinidazole (Tindamax) - a new anti-protozoal drug. Med Lett Drugs Ther. 2004 Aug 30;46(1190):70-2.
• [8] Comparison of various urine collection intervals for caffeine and dextromethorphan phenotyping in children. J Clin Pharmacol. 2004 Jul;44(7):708-14. doi: 10.1177/0091270004266624.
• [9] Dextromethorphan/quinidine: AVP 923, dextromethorphan/cytochrome P450-2D6 inhibitor, quinidine/dextromethorphan. Drugs R D. 2005;6(3):174-7.
• [10] Comparative contribution to dextromethorphan metabolism by cytochrome P450 isoforms in vitro: can dextromethorphan be used as a dual probe for both CTP2D6 and CYP3A activities? Drug Metab Dispos. 2001 Nov;29(11):1514-20.
• [11] Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009;48(11):689-723.
• [12] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [13] Characterization of dextromethorphan N-demethylation by human liver microsomes. Contribution of the cytochrome P450 3A (CYP3A) subfamily. Biochem Pharmacol. 1994 Jul 5;48(1):173-82.
• [14] Multiple human cytochromes contribute to biotransformation of dextromethorphan in-vitro: role of CYP2C9, CYP2C19, CYP2D6, and CYP3A. J Pharm Pharmacol. 1998 Sep;50(9):997-1004.
• [15] Enzymes in addition to CYP3A4 and 3A5 mediate N-demethylation of dextromethorphan in human liver microsomes. Biopharm Drug Dispos. 1999 Oct;20(7):341-6.
• [16] Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry. 2003 Dec 9;42(48):14284-92.
• [17] The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
• [18] Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets? Appl Microbiol Biotechnol. 2019 May;103(9):3597-3614.
• [19] Evidence of significant contribution from CYP3A5 to hepatic drug metabolism. Drug Metab Dispos. 2004 Dec;32(12):1434-45. doi: 10.1124/dmd.104.001313. Epub 2004 Sep 21.
• [20] Myoclonus after dextromethorphan administration in peritoneal dialysis. Ann Pharmacother. 2011 Jan;45(1):e1. doi: 10.1345/aph.1P301. Epub 2010 Dec 14.
• [21] Dextromethorphan - A widely-used cough suppressant - Induces local anaphylaxis via MRGPRX2 on mast cells. Chem Biol Interact. 2020 Oct 1;330:109248. doi: 10.1016/j.cbi.2020.109248. Epub 2020 Aug 29.
• [22] Effects of common antitussive drugs on the hERG potassium channel current. J Cardiovasc Pharmacol. 2008 Dec;52(6):494-9. doi: 10.1097/FJC.0b013e31818eec8d.
• [23] FDA label of Tinidazole. The 2020 official website of the U.S. Food and Drug Administration.
• [24] Overexpression, isotopic labeling, and spectral characterization of Enterobacter cloacae nitroreductase. Protein Expr Purif. 1998 Jun;13(1):53-60.
• [25] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.