Details of the Drug Combination

General Information of Drug Combination (ID: DCSL2S0)

• Drug Combination Name: Physostigmine + Scopolamine
• Indication: Nicotine dependence; Status: Discontinued [1]
• Component Drugs:
  Physostigmine (DM2N0TO): Small molecular drug
  Scopolamine (DMOM8AL): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Physostigmine

Disease Entry	ICD 11	Status	REF
Xerostomia	DA02.1	Discontinued in Phase 2	[2]

Physostigmine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (AChE)	TT1RS9F	ACES_HUMAN	Inhibitor	[5]

Physostigmine Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Decreases Activity	[6]
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[7]
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Decreases Activity	[8]
Neuronal acetylcholine receptor subunit beta-2 (CHRNB2)	OTNAT2M5	ACHB2_HUMAN	Affects Binding	[9]
Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4)	OT1H0ZXC	ACHA4_HUMAN	Affects Binding	[9]

Indication(s) of Scopolamine

Disease Entry	ICD 11	Status	REF
Addictive disorder	6C50-6C5Z	Approved	[3]
Allergic rhinitis	CA08.0	Approved	[4]
Common cold	CA00	Approved	[4]
Cough	MD12	Approved	[4]
Irritable bowel syndrome	DD91.0	Approved	[4]
Major depressive disorder	6A70.3	Approved	[4]
Mydriasis	LA11.62	Approved	[4]
Nausea	MD90	Approved	[3]
Peptic ulcer	DA61	Approved	[4]
Vasomotor/allergic rhinitis	CA08	Approved	[4]
Iridocyclitis	N.A.	Investigative	[4]
Uveitis	9A96.Z	Investigative	[4]

Scopolamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Muscarinic acetylcholine receptor (CHRM)	TTOXS3C	NOUNIPROTAC	Antagonist	[10]

Scopolamine Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Increases Activity	[11]
Choline O-acetyltransferase (CHAT)	OTEJWQ45	CLAT_HUMAN	Decreases Activity	[11]
Microtubule-associated protein 2 (MAP2)	OT6UYT3X	MTAP2_HUMAN	Decreases Expression	[12]
Neurofilament heavy polypeptide (NEFH)	OTMSCW5I	NFH_HUMAN	Decreases Expression	[12]
Neuromodulin (GAP43)	OT2OTGGV	NEUM_HUMAN	Decreases Expression	[12]
Neuronal acetylcholine receptor subunit beta-2 (CHRNB2)	OTNAT2M5	ACHB2_HUMAN	Affects Binding	[9]
Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4)	OT1H0ZXC	ACHA4_HUMAN	Affects Binding	[9]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Increases ADR	[13]
Histone deacetylase 2 (HDAC2)	OTUYVFKN	HDAC2_HUMAN	Increases ADR	[13]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006543)
• [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: 6598).
• [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: 330).
• [4] Scopolamine FDA Label
• [5] The effects of physostigmine on acetylcholinesterase activity of CSF plasma and brain. A comparison of intravenous and intraventricular administration in beagle dogs. Neuropharmacology. 1986 Oct;25(10):1167-77.
• [6] Monoclonal antibodies to fetal bovine serum acetylcholinesterase distinguish between acetylcholinesterases from ruminant and non-ruminant species. Chem Biol Interact. 2020 Oct 1;330:109225. doi: 10.1016/j.cbi.2020.109225. Epub 2020 Aug 12.
• [7] In vitro kinetic interactions of pyridostigmine, physostigmine and soman with erythrocyte and muscle acetylcholinesterase from different species. Toxicol Lett. 2011 Sep 25;206(1):41-6.
• [8] Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin. J Biol Chem. 1997 Jun 6;272(23):14769-75. doi: 10.1074/jbc.272.23.14769.
• [9] 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.
• [10] The amygdala modulates morphine-induced state-dependent memory retrieval via muscarinic acetylcholine receptors. Neuroscience. 2009 May 5;160(2):255-63.
• [11] Effect of Kangshuai Yizhi Formula I on learning and memory dysfunction induced by scopolamine in mice. Chin J Integr Med. 2010 Jun;16(3):252-7.
• [12] Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells. PLoS One. 2011;6(11):e27265. doi: 10.1371/journal.pone.0027265. Epub 2011 Nov 11.
• [13] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.