Details of the Drug Combination

General Information of Drug Combination (ID: DCY9BK0)

• Drug Combination Name: Mecamylamine + Dexmedetomidine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Mecamylamine (DMGQFYB): Small molecular drug
  Dexmedetomidine (DM93L4X): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 10.19
  Bliss Independence Score: 10.19
  Loewe Additivity Score: 24.19
  LHighest Single Agent (HSA) Score: 24.2

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Mecamylamine

Disease Entry	ICD 11	Status	REF
Essential hypertension	BA00	Approved	[2]

Mecamylamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Nicotinic acetylcholine receptor (nAChR)	TTJSZTB	NOUNIPROTAC	Antagonist	[6]

Mecamylamine Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dihydrofolate reductase (DHFR)	OT3DVIGM	DYR_HUMAN	Decreases Expression	[5]
Receptor-type tyrosine-protein phosphatase alpha (PTPRA)	OTZA82J1	PTPRA_HUMAN	Decreases Expression	[5]
Contactin-1 (CNTN1)	OT7RNPEY	CNTN1_HUMAN	Increases Expression	[5]
Fasciculation and elongation protein zeta-1 (FEZ1)	OTWCXPRE	FEZ1_HUMAN	Decreases Expression	[5]
Lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF)	OTT5JX1F	LITAF_HUMAN	Decreases Expression	[5]
Echinoderm microtubule-associated protein-like 4 (EML4)	OTJC45TA	EMAL4_HUMAN	Decreases Expression	[5]
Stress-induced-phosphoprotein 1 (STIP1)	OT7TXLOX	STIP1_HUMAN	Decreases Expression	[7]
Golgin subfamily A member 4 (GOLGA4)	OTCMEHNJ	GOGA4_HUMAN	Increases Expression	[7]

Indication(s) of Dexmedetomidine

Disease Entry	ICD 11	Status	REF
Irritability	MB24	Approved	[3]
Obstructive sleep apnea	7A41	Approved	[4]
Traumatic brain injury	NA07.Z	Approved	[4]
Respiratory failure	CB41	Investigative	[4]

Dexmedetomidine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor Alpha-2 (ADRA2)	TTQ8AFT	NOUNIPROTAC	Agonist	[8]

Dexmedetomidine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[9]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[10]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[11]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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: 521).
• [4] Dexmedetomidine FDA Label
• [5] Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. J Biol Chem. 2003 May 2;278(18):15633-40.
• [6] Mecamylamine (Inversine): an old antihypertensive with new research directions. J Hum Hypertens. 2002 Jul;16(7):453-7.
• [7] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [8] Dexmedetomidine in intensive care unit: a study of hemodynamic changes. Middle East J Anesthesiol. 2002 Oct;16(6):587-95.
• [9] Predominant role of peripheral catecholamines in the stress-induced modulation of CYP1A2 inducibility by benzo(alpha)pyrene. Basic Clin Pharmacol Toxicol. 2008 Jan;102(1):35-44.
• [10] Impact of CYP2A6 gene polymorphism on the pharmacokinetics of dexmedetomidine for premedication. Expert Rev Clin Pharmacol. 2018 Sep;11(9):917-922.
• [11] Metabolic stability and determination of cytochrome P450 isoenzymes' contribution to the metabolism of medetomidine in dog liver microsomes. Biomed Chromatogr. 2010 Aug;24(8):868-77.