Details of the Drug Combination

General Information of Drug Combination (ID: DCH0JYQ)

• Drug Combination Name: Eszopiclone + Venlafaxine
• Indication: Major Depressive Disorder; Status: Phase 1 [1]
• Component Drugs:
  Eszopiclone (DM8RZ9H): Small molecular drug
  Venlafaxine (DMR6QH0): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Eszopiclone

Disease Entry	ICD 11	Status	REF
Insomnia	7A00-7A0Z	Approved	[2]

Eszopiclone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Translocator protein (TSPO)	TTPTXIN	TSPO_HUMAN	Agonist	[5]

Eszopiclone Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[7]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[6]

Indication(s) of Venlafaxine

Disease Entry	ICD 11	Status	REF
Anxiety disorder	6B00-6B0Z	Approved	[3]
Depression	6A70-6A7Z	Approved	[4]
Major depressive disorder	6A70.3	Approved	[3]
Panic disorder	6B01	Approved	[3]

Venlafaxine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[8]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[8]

Venlafaxine Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[9]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[10]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[10]

Venlafaxine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases ADR	[11]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases ADR	[12]

References

• [1] ClinicalTrials.gov (NCT00435279) A Study of Eszopiclone Co-administered With Venlafaxine in Subjects With Major Depressive Disorder and Insomnia
• [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: 7429).
• [3] Venlafaxine 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: 7321).
• [5] New hypnotics: perspectives from sleep physiology. Vertex. 2007 Jul-Aug;18(74):294-9.
• [6] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [7] Eszopiclone, a nonbenzodiazepine sedative-hypnotic agent for the treatment of transient and chronic insomnia. Clin Ther. 2006 Apr;28(4):491-516.
• [8] Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.
• [9] The associations between CYP2D6 metabolizer status and pharmacokinetics and clinical outcomes of venlafaxine: a systematic review and meta-analysis. Pharmacopsychiatry. 2019 Sep;52(5):222-231.
• [10] O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacology. 1999 May;20(5):480-90.
• [11] CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. J Clin Pharm Ther. 2006 Oct;31(5):493-502.
• [12] ABCB1 gene variants influence tolerance to selective serotonin reuptake inhibitors in a large sample of Dutch cases with major depressive disorder. Pharmacogenomics J. 2013 Aug;13(4):349-53.