Details of the Drug Combination

General Information of Drug Combination (ID: DCQCBAV)

• Drug Combination Name: Pargyline + Galantamine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Pargyline (DMM0HR1): Small molecular drug
  Galantamine (DMEO794): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 0.52
  Bliss Independence Score: 0.52
  Loewe Additivity Score: 15.78
  LHighest Single Agent (HSA) Score: 15.79

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pargyline

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[2]
Muscular dystrophy	8C70	Patented	[3]
Skin imperfections	EK71	Patented	[3]

Pargyline Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Monoamine oxidase (MAO)	TT32XQJ	NOUNIPROTAC	Inhibitor	[3]
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Inhibitor	[6]

Pargyline Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Decreases Activity	[7]
Amine oxidase B (MAOB)	OTTDFM1O	AOFB_HUMAN	Decreases Activity	[8]

Indication(s) of Galantamine

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Approved	[4]
Traumatic brain injury	NA07.Z	Approved	[5]

Galantamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (AChE)	TT1RS9F	ACES_HUMAN	Inhibitor	[9]

Galantamine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[10]

Galantamine Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Decreases Activity	[11]
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Decreases Activity	[12]
Neuronal acetylcholine receptor subunit beta-2 (CHRNB2)	OTNAT2M5	ACHB2_HUMAN	Affects Binding	[13]
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[14]
Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4)	OT1H0ZXC	ACHA4_HUMAN	Affects Binding	[13]

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] Novel monoamine oxidase inhibitors: a patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):91-110.
• [4] 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: 6693).
• [5] Galantamine FDA Label
• [6] Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells. Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H821-8.
• [7] Evaluation of metabolism dependent inhibition of CYP2B6 mediated bupropion hydroxylation in human liver microsomes by monoamine oxidase inhibitors and prediction of potential as perpetrators of drug interaction. Chem Biol Interact. 2015 Mar 25;230:9-20.
• [8] Combining initro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. Chem Biol Interact. 2016 Jul 25;254:135-45.
• [9] [From symptomatic to disease modifying therapy Recent developments in the pharmacotherapy of Alzheimer's disease]. Fortschr Neurol Psychiatr. 2009 Jun;77(6):326-33.
• [10] Clinical pharmacokinetics of galantamine. Clin Pharmacokinet. 2003;42(15):1383-92.
• [11] Lichens of parmelioid clade as promising multitarget neuroprotective agents. Chem Res Toxicol. 2019 Jun 17;32(6):1165-1177.
• [12] Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors. Chem Biol Interact. 2013 Mar 25;203(1):226-30.
• [13] Cholinergic drugs potentiate human nicotinic alpha4beta2 acetylcholine receptors by a competitive mechanism. Eur J Pharmacol. 2005 Feb 21;509(2-3):97-108. doi: 10.1016/j.ejphar.2004.12.037.
• [14] Potencies and selectivities of inhibitors of acetylcholinesterase and its molecular forms in normal and Alzheimer's disease brain. Acta Biol Hung. 2003;54(2):183-9. doi: 10.1556/ABiol.54.2003.2.7.