Details of the Drug Combination

General Information of Drug Combination (ID: DCDONMW)

• Drug Combination Name: Caffeine + Dipyridamole
• Indication: Cardiovascular Disease; Status: Phase 1 [1]
• Component Drugs:
  Caffeine (DMKBJWP): Small molecular drug
  Dipyridamole (DMXY30O): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Caffeine

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[2]
Back pain	ME84.Z	Approved	[2]
Cluster headache	8A81.0	Approved	[2]
Common cold	CA00	Approved	[2]
Dysmenorrhea	GA34.3	Approved	[2]
Headache	8A80-8A84	Approved	[2]
Migraine disorder	N.A.	Approved	[2]
Orthostatic hypotension	BA21	Approved	[3]
Pain	MG30-MG3Z	Approved	[2]

Caffeine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adenosine A2a receptor (ADORA2A)	TTM2AOE	AA2AR_HUMAN	Antagonist	[6]
Adenosine A1 receptor (ADORA1)	TTK25J1	AA1R_HUMAN	Antagonist	[6]

Caffeine Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[8]
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[10]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[11]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[12]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[13]
Cytochrome P450 1B1 (CYP1B1)	DE9QHP6	CP1B1_HUMAN	Metabolism	[14]

Caffeine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases ADR	[15]
Metallothionein-1A (MT1A)	OTKBH52X	MT1A_HUMAN	Increases ADR	[16]

Indication(s) of Dipyridamole

Disease Entry	ICD 11	Status	REF
Atrial fibrillation	BC81.3	Approved	[4]
Chronic heart failure	BD1Z	Approved	[4]
Hypertension	BA00-BA04	Approved	[5]
Malignant essential hypertension	BA00	Approved	[4]

Dipyridamole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phosphodiesterase 5A (PDE5A)	TTJ0IQB	PDE5A_HUMAN	Modulator	[18]

Dipyridamole Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[19]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[20]

Dipyridamole Interacts with 16 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A)	OTT8Q1AP	PDE5A_HUMAN	Decreases Activity	[21]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Activity	[21]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[22]
ATP-binding cassette sub-family C member 4 (ABCC4)	OTO27PAL	MRP4_HUMAN	Decreases Activity	[23]
Tissue-type plasminogen activator (PLAT)	OTQPDNAB	TPA_HUMAN	Increases Secretion	[24]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[25]
Alpha-1-acid glycoprotein 1 (ORM1)	OTZKSBRE	A1AG1_HUMAN	Affects Binding	[26]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[27]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[28]
CD40 ligand (CD40LG)	OT75Z6A6	CD40L_HUMAN	Decreases Secretion	[29]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[30]
Calcipressin-1 (RCAN1)	OT1MVXC7	RCAN1_HUMAN	Affects Binding	[31]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[30]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[32]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Increases Expression	[33]
Equilibrative nucleoside transporter 1 (SLC29A1)	OTLOOZZS	S29A1_HUMAN	Decreases Activity	[34]

References

• [1] ClinicalTrials.gov (NCT00430170) Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?
• [2] Caffeine 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: 407).
• [4] Dipyridamole FDA Label
• [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: 4807).
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• [23] Expression of multidrug transporter MRP4/ABCC4 is a marker of poor prognosis in neuroblastoma and confers resistance to irinotecan in vitro. Mol Cancer Ther. 2005 Apr;4(4):547-53. doi: 10.1158/1535-7163.MCT-04-0161.
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• [26] Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. doi: 10.1097/00008571-199610000-00004.
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