Details of the Drug Combination

General Information of Drug Combination (ID: DCZ4CHL)

• Drug Combination Name: Duloxetine + Desvenlafaxine
• Indication: Depression; Status: Phase 1 [1]
• Component Drugs:
  Duloxetine (DM9BI7M): Small molecular drug
  Desvenlafaxine (DMHD4PE): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Duloxetine

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[2]
Major depressive disorder	6A70.3	Approved	[3]
Stress urinary incontinence	MF50.20	Approved	[3]
Traumatic brain injury	NA07.Z	Approved	[3]

Duloxetine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[5]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[5]

Duloxetine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[6]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[6]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[6]

Duloxetine Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1)	OTZKVLVJ	CP17A_HUMAN	Decreases Activity	[7]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[8]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[9]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[10]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[11]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Affects Localization	[10]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[9]

Indication(s) of Desvenlafaxine

Disease Entry	ICD 11	Status	REF
Major depressive disorder	6A70.3	Approved	[4]
Menopause symptom	GA30.0	Phase 3	[4]

Desvenlafaxine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Modulator	[12]

References

• [1] ClinicalTrials.gov (NCT02320240) Serotonin-norepinephrine Reuptake Inhibitors and Acute Kidney Injury
• [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: 202).
• [3] Duloxetine FDA Label
• [4] 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: 7158).
• [5] Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42.
• [6] Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94.
• [7] Steroidogenic disruptive effects of the serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol in the H295R cell assay and in a recombinant CYP17 assay. Toxicol In Vitro. 2018 Mar;47:63-71.
• [8] Hyperprolactinemia and galactorrhea induced by serotonin and norepinephrine reuptake inhibiting antidepressants. Am J Psychiatry. 2007 Jul;164(7):1121-2. doi: 10.1176/ajp.2007.164.7.1121a.
• [9] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [10] Duloxetine Protects Human Neuroblastoma Cells from Oxidative Stress-Induced Cell Death Through Akt/Nrf-2/HO-1 Pathway. Neurochem Res. 2018 Feb;43(2):387-396. doi: 10.1007/s11064-017-2433-3. Epub 2017 Nov 13.
• [11] Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
• [12] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.