Details of the Drug Combination

General Information of Drug Combination (ID: DCH97QT)

• Drug Combination Name: Venlafaxine + Fingolimod
• Indication: Depression; Status: Phase 1 [1]
• Component Drugs:
  Venlafaxine (DMR6QH0): Small molecular drug
  Fingolimod (DM5JVAN): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Venlafaxine

Disease Entry	ICD 11	Status	REF
Anxiety disorder	6B00-6B0Z	Approved	[2]
Depression	6A70-6A7Z	Approved	[3]
Major depressive disorder	6A70.3	Approved	[2]
Panic disorder	6B01	Approved	[2]

Venlafaxine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[7]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[7]

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	[8]
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]

Indication(s) of Fingolimod

Disease Entry	ICD 11	Status	REF
Multiple sclerosis	8A40	Approved	[4]
Primary progressive multiple sclerosis	8A40.1	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[6]

Fingolimod Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sphingosine-1-phosphate receptor 1 (S1PR1)	TT9JZCK	S1PR1_HUMAN	Modulator	[13]

Fingolimod Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 4F2 (CYP4F2)	DE3GT9C	CP4F2_HUMAN	Metabolism	[14]
Cytochrome P450 4F12 (CYP4F12)	DED26GV	CP4FC_HUMAN	Metabolism	[14]

References

• [1] ClinicalTrials.gov (NCT01436643) Combination of Antidepressants and Fingolimod Relapsing-remitting Multiple Sclerosis (RRMS) Patients With Depression
• [2] Venlafaxine 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: 7321).
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] 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: 2407).
• [6] ClinicalTrials.gov (NCT04280588) Fingolimod in COVID-19
• [7] Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.
• [8] 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.
• [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.
• [13] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [14] CYP4F enzymes are responsible for the elimination of fingolimod (FTY720), a novel treatment of relapsing multiple sclerosis. Drug Metab Dispos. 2011 Feb;39(2):191-8.