Details of the Drug Combination

General Information of Drug Combination (ID: DCVMM8X)

• Drug Combination Name: Buprenorphine + Methadone
• Indication: Substance-related Disorders; Status: Phase 1 [1]
• Component Drugs:
  Buprenorphine (DMPRI8G): Small molecular drug
  Methadone (DMTW6IU): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Buprenorphine

Disease Entry	ICD 11	Status	REF
Opioid dependence	6C43.2Z	Approved	[2]
Pain	MG30-MG3Z	Approved	[3]
Psychiatric disorder	6E8Z	Phase 3	[4]
Migraine	8A80	Phase 2	[5]
Chronic pain	MG30	Investigative	[2]

Buprenorphine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Agonist	[9]

Buprenorphine Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[11]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[13]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[14]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Metabolism	[15]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[16]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[14]

Buprenorphine Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Activity	[17]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Activity	[17]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Increases Expression	[18]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[18]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[18]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Decreases Expression	[18]

Indication(s) of Methadone

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[6]
Dry cough	MD12	Approved	[7]
Pain	MG30-MG3Z	Approved	[6]

Methadone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor (OPR)	TTN4QDT	NOUNIPROTAC	Agonist	[19]

Methadone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[20]

Methadone Interacts with 10 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[21]
Aromatase (CYP19A1)	DEQX145	CP19A_HUMAN	Metabolism	[22]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[23]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[21]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[21]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Metabolism	[24]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[21]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[21]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[21]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[21]

Methadone Interacts with 16 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Activity	[25]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[26]
Toll-like receptor 4 (TLR4)	OTP7ML3S	TLR4_HUMAN	Affects Binding	[27]
Phospholipase D2 (PLD2)	OT86I3WH	PLD2_HUMAN	Increases Activity	[18]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[28]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Response To Substance	[29]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Increases Expression	[18]
Alpha-1-acid glycoprotein 2 (ORM2)	OTRJGZP8	A1AG2_HUMAN	Affects Binding	[30]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[31]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[18]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[18]
Leptin (LEP)	OT5Q7ODW	LEP_HUMAN	Increases Expression	[32]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Decreases Expression	[18]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[33]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Affects Localization	[33]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[34]

References

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• [2] Buprenorphine FDA Label
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• [6] Methadone FDA Label
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