Details of the Drug Combination

General Information of Drug Combination (ID: DCUH0KL)

• Drug Combination Name: Naloxone + Clonidine
• Indication: Experimental Pain Perception; Status: Phase 1 [1]
• Component Drugs:
  Naloxone (DM3FXMA): Small molecular drug
  Clonidine (DM6RZ9Q): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Naloxone

Disease Entry	ICD 11	Status	REF
Narcotic depression	6A7Z	Approved	[2]
Pain	MG30-MG3Z	Approved	[3]
Pruritus	EC90	Phase 3	[4]
Respiratory depression	MD11.5	Phase 3	[5]
Opioid dependence	6C43.2Z	Phase 1	[5]

Naloxone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Antagonist	[10]

Naloxone Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[11]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Decreases Expression	[12]
Vasopressin-neurophysin 2-copeptin (AVP)	OTAVZ76K	NEU2_HUMAN	Decreases Secretion	[13]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Expression	[14]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[15]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Affects Expression	[16]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Response To Substance	[17]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[18]
Liver carboxylesterase 1 (CES1)	OT9L0LR8	EST1_HUMAN	Affects Binding	[19]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Decreases Response To Substance	[20]

Indication(s) of Clonidine

Disease Entry	ICD 11	Status	REF
Attention deficit hyperactivity disorder	6A05.Z	Approved	[6]
Hypertension	BA00-BA04	Approved	[7]
Neonatal abstinence syndrome	N.A.	Approved	[6]
Diabetic neuropathy	8C0Z	Phase 3	[8]

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	[21]
Membrane copper amine oxidase (AOC3)	TT7HC21	AOC3_HUMAN	Inhibitor	[22]

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	[23]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[24]
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[24]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[24]

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	[25]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[25]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[25]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[25]

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	[26]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases ADR	[26]
G protein-activated inward rectifier potassium channel 1 (KCNJ3)	OTHQG16J	KCNJ3_HUMAN	Increases ADR	[26]
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Increases Expression	[27]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[28]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Expression	[29]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[30]
Somatotropin (GH1)	OT92RTRD	SOMA_HUMAN	Increases Expression	[31]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Secretion	[32]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Decreases Expression	[33]
Apolipoprotein A-II (APOA2)	OTQ3HGTC	APOA2_HUMAN	Decreases Expression	[33]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[27]
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)	OTVLI4DD	TNAP3_HUMAN	Increases Expression	[34]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[35]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[27]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Activity	[27]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[27]
Tumor protein D52 (TPD52)	OTPKSK43	TPD52_HUMAN	Increases Expression	[34]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[27]
Programmed cell death protein 4 (PDCD4)	OTZ6NXUX	PDCD4_HUMAN	Decreases Expression	[34]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Increases Expression	[27]
Delta-type opioid receptor (OPRD1)	OT164PA1	OPRD_HUMAN	Increases ADR	[26]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases ADR	[26]
Kappa-type opioid receptor (OPRK1)	OTXCZF4L	OPRK_HUMAN	Increases ADR	[26]

References

• [1] ClinicalTrials.gov (NCT01851486) The Relationships Between the Noradrenergic, Opioid and Pain System
• [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: 1668).
• [3] Naloxone FDA Label
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Clonidine FDA Label
• [7] 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: 516).
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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