Details of the Drug Combination

General Information of Drug Combination (ID: DCD09A2)

• Drug Combination Name: Epinephrine + Clonidine
• Indication: Total Hip and Knee Arthroplasty; Status: Phase 4 [1]
• Component Drugs:
  Epinephrine (DM3KJBC): Small molecular drug
  Clonidine (DM6RZ9Q): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Epinephrine

Disease Entry	ICD 11	Status	REF
Acute asthma	CA23	Approved	[2]
Allergy	4A80-4A85	Approved	[3]
Anaphylaxis	N.A.	Approved	[2]
Bronchiectasis	CA24	Approved	[2]
Bronchitis	CA20	Approved	[2]
Periodontitis	DA0C	Approved	[2]
Pulmonary emphysema	CA21.Z	Approved	[2]
Severe asthma	CA23	Approved	[2]
Asthma	CA23	Investigative	[2]

Epinephrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Agonist	[7]

Epinephrine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[8]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[9]

Epinephrine Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[10]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[11]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[12]
Catechol O-methyltransferase (COMT)	DEV3T4A	COMT_HUMAN	Metabolism	[13]
Monoamine oxidase type A (MAO-A)	DERE4TU	AOFA_HUMAN	Metabolism	[14]

Epinephrine Interacts with 33 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Increases Methylation	[15]
Solute carrier family 22 member 3 (SLC22A3)	OTQYGVXX	S22A3_HUMAN	Increases Uptake	[16]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Increases Expression	[17]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[17]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Increases Expression	[18]
Integrin alpha-V (ITGAV)	OTAM7JTR	ITAV_HUMAN	Increases Expression	[18]
Cathepsin K (CTSK)	OTT3YX5O	CATK_HUMAN	Increases Expression	[18]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[19]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[20]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Activity	[21]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Decreases Cleavage	[22]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[22]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Increases Expression	[22]
Pyruvate kinase PKM (PKM)	OTLHHMC2	KPYM_HUMAN	Increases Expression	[22]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Increases Activity	[23]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[24]
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Increases Activity	[23]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Increases Activity	[23]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[24]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[24]
Hexokinase-2 (HK2)	OTC0GCQO	HXK2_HUMAN	Increases Expression	[22]
Ephrin type-A receptor 4 (EPHA4)	OT3AMK0C	EPHA4_HUMAN	Increases Phosphorylation	[25]
Hormone-sensitive lipase (LIPE)	OTMMVJ8A	LIPS_HUMAN	Increases Activity	[26]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[22]
P2X purinoceptor 7 (P2RX7)	OTNJ9XPL	P2RX7_HUMAN	Decreases Activity	[27]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Increases ADR	[28]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Response To Substance	[29]
Sulfotransferase 1A3 (SULT1A4)	OTHJ8WWV	ST1A3_HUMAN	Increases Sulfation	[30]
Glutathione reductase, mitochondrial (GSR)	OTM2TUYM	GSHR_HUMAN	Increases ADR	[28]
Neuron-specific vesicular protein calcyon (CALY)	OTQ7EMPU	CALY_HUMAN	Decreases Secretion	[31]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases ADR	[28]
Equilibrative nucleoside transporter 4 (SLC29A4)	OTWTZXMX	S29A4_HUMAN	Increases Uptake	[16]
Alpha-2A adrenergic receptor (ADRA2A)	OTZFGOTP	ADA2A_HUMAN	Increases ADR	[28]

Indication(s) of Clonidine

Disease Entry	ICD 11	Status	REF
Attention deficit hyperactivity disorder	6A05.Z	Approved	[4]
Hypertension	BA00-BA04	Approved	[5]
Neonatal abstinence syndrome	N.A.	Approved	[4]
Diabetic neuropathy	8C0Z	Phase 3	[6]

Clonidine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor Alpha-2 (ADRA2)	TTQ8AFT	NOUNIPROTAC	Agonist	[32]
Membrane copper amine oxidase (AOC3)	TT7HC21	AOC3_HUMAN	Inhibitor	[33]

Clonidine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[34]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[35]
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[35]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[35]

Clonidine Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[36]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[36]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[36]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[36]

Clonidine Interacts with 24 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases ADR	[28]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases ADR	[28]
G protein-activated inward rectifier potassium channel 1 (KCNJ3)	OTHQG16J	KCNJ3_HUMAN	Increases ADR	[28]
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Increases Expression	[37]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[38]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Expression	[39]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[40]
Somatotropin (GH1)	OT92RTRD	SOMA_HUMAN	Increases Expression	[41]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Secretion	[42]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Decreases Expression	[43]
Apolipoprotein A-II (APOA2)	OTQ3HGTC	APOA2_HUMAN	Decreases Expression	[43]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[37]
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)	OTVLI4DD	TNAP3_HUMAN	Increases Expression	[44]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[45]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[37]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Activity	[37]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[37]
Tumor protein D52 (TPD52)	OTPKSK43	TPD52_HUMAN	Increases Expression	[44]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[37]
Programmed cell death protein 4 (PDCD4)	OTZ6NXUX	PDCD4_HUMAN	Decreases Expression	[44]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Increases Expression	[37]
Delta-type opioid receptor (OPRD1)	OT164PA1	OPRD_HUMAN	Increases ADR	[28]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases ADR	[28]
Kappa-type opioid receptor (OPRK1)	OTXCZF4L	OPRK_HUMAN	Increases ADR	[28]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Hip Dysplasia	DC0MOL2	N. A.	Phase 4	[46]

References

• [1] ClinicalTrials.gov (NCT02543801) A Clinical Trial of Two Periarticular Multimodal Drug Injections in Total Hip and Knee Arthroplasty
• [2] Epinephrine FDA Label
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• [4] Clonidine FDA Label
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• [46] ClinicalTrials.gov (NCT02365961) Hip Scope Fascia-iliaca (FI) Block Study