Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM2N0TO)

• Drug Name: Physostigmine Drug Info
• Synonyms: Xalieve; Acetylcholinesterase inhibitor (dry mouth), Calabar; Physostigmine (local acting gel, xerostomia); Physostigmine (buccal, xerostomia), Calabar; Physostigmine (local acting gel, xerostomia), Calabar

Indication

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

• Cross-matching ID:
  PubChem CID: 5983
  ChEBI ID: CHEMBL94
  CAS Number: CAS 57-47-6
  TTD Drug ID: DM2N0TO

Molecule-Related Drug Atlas

Drug(s) Targeting Acetylcholinesterase (AChE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tacrine	DM51FY6	Alzheimer disease	8A20	Approved	[4]
Donepezil	DMIYG7Z	Advanced cancer	2A00-2F9Z	Approved	[5]
Malathion	DMXZ84M	Pediculus capitis infestation	1G00.0	Approved	[6]
Galantamine	DMEO794	Alzheimer disease	8A20	Approved	[7]
Huperzine A	DMMAWLU	Alzheimer disease	8A20	Approved	[8]
Neostigmine	DM6T2J3	Myasthenia gravis	8C6Y	Approved	[9]
YM443	DMNZCI1	Functional dyspepsia	DD90.3	Approved	[10]
Ambenonium	DMOP0BL	Myasthenia gravis	8C6Y	Approved	[11]
Demecarium bromide	DMAYEU1	Open-angle glaucoma	9C61	Approved	[12]
Isoflurophate	DMBSK7X	Glaucoma/ocular hypertension	9C61	Approved	[13]

Drug(s) Affected By Cocaine esterase (CES2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[14]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[15]
Dextropropoxyphene	DM23HCX	Pain	MG30-MG3Z	Approved	[16]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[17]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
Tacrine	DM51FY6	Alzheimer disease	8A20	Approved	[19]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[20]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[21]
Testosterone enanthate	DMB6871	N. A.	N. A.	Approved	[22]
Cantharidin	DMBP5N3	Molluscum contagiosum infection	1E76	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Acetylcholinesterase (AChE)	TT1RS9F	ACES_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Gene/Protein Processing	[3]

References

• [1] 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).
• [2] 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.
• [3] 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.
• [4] Evidence that the clinical effects of cholinesterase inhibitors are related to potency and targeting of action. Int J Clin Pract Suppl. 2002 Jun;(127):6-19.
• [5] 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. (Target id: 2465).
• [6] Acetylcholinesterase activity in Corbicula fluminea Mull., as a biomarker of organophosphate pesticide pollution in Pinacanauan River, Philippines. Environ Monit Assess. 2010 Jun;165(1-4):331-40.
• [7] [From symptomatic to disease modifying therapy Recent developments in the pharmacotherapy of Alzheimer's disease]. Fortschr Neurol Psychiatr. 2009 Jun;77(6):326-33.
• [8] Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after hypoxia-ischemia. Brain Res. 2002 Sep 13;949(1-2):162-70.
• [9] Screening of acetylcholinesterase inhibitors by CE after enzymatic reaction at capillary inlet. J Sep Sci. 2009 May;32(10):1748-56.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [11] Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens. Neuropsychopharmacology. 2008 Aug;33(9):2158-66.
• [12] The effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase levels in normal dogs. Vet Ophthalmol. 2003 Mar;6(1):23-5.
• [13] Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators. Chem Biol. 2003 Jun;10(6):491-502.
• [14] Dexamethasone differentially regulates expression of carboxylesterase genes in humans and rats. Drug Metab Dispos. 2000 Feb;28(2):186-91.
• [15] Transcriptional activation of the carboxylesterase 2 gene by the p53 pathway. Cancer Biol Ther. 2006 Nov;5(11):1450-6.
• [16] Binding and hydrolysis of meperidine by human liver carboxylesterase hCE-1. J Pharmacol Exp Ther. 1999 Jul;290(1):314-8.
• [17] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [18] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [19] Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors. Chem Biol Interact. 2013 Mar 25;203(1):226-30.
• [20] Photochemotherapeutic agent 8-methoxypsoralen induces cytochrome P450 3A4 and carboxylesterase HCE2: evidence on an involvement of the pregnane X receptor. Toxicol Sci. 2007 Jan;95(1):13-22.
• [21] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [22] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [23] Hepatoxicity mechanism of cantharidin-induced liver LO2 cells by LC-MS metabolomics combined traditional approaches. Toxicol Lett. 2020 Oct 15;333:49-61. doi: 10.1016/j.toxlet.2020.07.024. Epub 2020 Jul 26.