Details of the Drug Combination

General Information of Drug Combination (ID: DC7LCRZ)

• Drug Combination Name: Ramelteon + Eszopiclone
• Indication: Marijuana Dependence; Status: Phase 1 [1]
• Component Drugs:
  Ramelteon (DM7IW9J): Small molecular drug
  Eszopiclone (DM8RZ9H): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ramelteon

Disease Entry	ICD 11	Status	REF
Insomnia	7A00-7A0Z	Approved	[2]
Circadian rhythm sleep disorder	7A60-7A65	Terminated	[2]

Ramelteon Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Melatonin receptor type 1B (MTNR1B)	TT32JK8	MTR1B_HUMAN	Modulator	[5]
Melatonin receptor type 1A (MTNR1A)	TT0WAIE	MTR1A_HUMAN	Modulator	[5]

Ramelteon Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[6]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[7]

Ramelteon Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Retinal dehydrogenase 2 (ALDH1A2)	OTJB560Z	AL1A2_HUMAN	Decreases Expression	[4]
Homeobox protein Hox-B7 (HOXB7)	OTC7WYU8	HXB7_HUMAN	Increases Expression	[4]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Decreases Expression	[4]
Homeobox protein MOX-1 (MEOX1)	OTJEMT2D	MEOX1_HUMAN	Decreases Expression	[4]
Fibroblast growth factor 8 (FGF8)	OTFU0IUW	FGF8_HUMAN	Decreases Expression	[4]
Mesoderm posterior protein 2 (MESP2)	OT7H4LYA	MESP2_HUMAN	Increases Expression	[4]
Oligodendrocyte transcription factor 3 (OLIG3)	OTU8XLAF	OLIG3_HUMAN	Decreases Expression	[4]
Eyes absent homolog 1 (EYA1)	OTHU807A	EYA1_HUMAN	Decreases Expression	[4]

Indication(s) of Eszopiclone

Disease Entry	ICD 11	Status	REF
Insomnia	7A00-7A0Z	Approved	[3]

Eszopiclone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Translocator protein (TSPO)	TTPTXIN	TSPO_HUMAN	Agonist	[8]

Eszopiclone Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[10]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[9]

References

• [1] ClinicalTrials.gov (NCT00893269) The Effect of Marijuana and Prescription Medications in Mood, Performance and Sleep
• [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: 1356).
• [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: 7429).
• [4] Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
• [5] MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014 Apr 24;57(8):3161-85.
• [6] Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. Drug Metab Dispos. 2010 Aug;38(8):1381-91.
• [7] Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical applications. J Cent Nerv Syst Dis. 2011 Apr 12;3:51-65.
• [8] New hypnotics: perspectives from sleep physiology. Vertex. 2007 Jul-Aug;18(74):294-9.
• [9] 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.
• [10] Eszopiclone, a nonbenzodiazepine sedative-hypnotic agent for the treatment of transient and chronic insomnia. Clin Ther. 2006 Apr;28(4):491-516.