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

General Information of Drug (ID: DM0J92L)

• Drug Name: Benactyzine Drug Info
• Synonyms: BENACTYZINE; Benactyzin; Benzactyzine; 302-40-9; Diethylaminoethyl benzilate; Benactizina; Benactizina [DCIT]; Benactizina [Italian]; 2-(Diethylamino)ethyl benzilate; Benactyzine [INN:BAN]; Benactyzinum [INN-Latin]; Benacticina [INN-Spanish]; 2-Diethylaminoethyl benzilate; UNII-595EG71R3F; 2-(Diethylamino)ethyl diphenylglycolate; HSDB 3292; Benzilic acid, 2-(diethylamino)ethyl ester; EINECS 206-123-8; Diphenylglycolic acid 2-(diethylamino)ethyl ester; BRN 2156821; Benzilic acid beta-diethylaminoethyl ester; CHEMBL70352

Indication

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Withdrawn from market	[1]

• Cross-matching ID:
  PubChem CID: 9330
  ChEBI ID: CHEBI:94775
  CAS Number: CAS 302-40-9
  TTD Drug ID: DM0J92L

Molecule-Related Drug Atlas

Drug(s) Targeting Muscarinic acetylcholine receptor M5 (CHRM5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Promazine	DMZAL7W	Acute intermittent hepatic porphyria	5C58.11	Approved	[4]
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[5]
Pilocarpine	DMV9ADG	Glaucoma/ocular hypertension	9C61	Approved	[6]
Anisodine	DMNOSWU	Central and peripheral nervous disease	8A04-8E7Z	Approved	[7]
Atropine	DMEN6X7	Organophosphate poisoning	NE6Z	Approved	[8]
Propiverine	DMUWBIJ	Urinary incontinence	MF50.2	Approved	[9]
Umeclidinium	DM4E8O9	Chronic obstructive pulmonary disease	CA22	Approved	[10]
Cimetropium bromide	DMZHPNE	Gastric motility disorder	DA21	Approved	[11]
Butylscopolamine	DMZKXB7	Dysmenorrhea	GA34.3	Approved	[12]
Trospium	DMX6RTG	Overactive bladder	GC50.0	Approved	[13]

Drug(s) Affected By Potassium voltage-gated channel subfamily H member 2 (KCNH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metoclopramide	DMFA5MY	Nausea	MD90	Approved	[14]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[16]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[17]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[17]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[18]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[19]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[20]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[21]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[17]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Muscarinic acetylcholine receptor M5 (CHRM5)	TTH18TF	ACM5_HUMAN	Antagonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[3]

References

• [1] Benactyzine as an aid in treatment of anxiety states; preliminary report. Br Med J. 1957 Feb 9;1(5014):306-10.
• [2] The muscarinic antagonists aprophen and benactyzine are noncompetitive inhibitors of the nicotinic acetylcholine receptor. Mol Pharmacol. 1987 Nov;32(5):678-85.
• [3] Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
• [4] Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12.
• [5] Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J Med Chem. 1993 Apr 2;36(7):842-7.
• [6] Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L340-6.
• [7] Medicinal plants in therapy. Bull World Health Organ. 1985;63(6):965-81.
• [8] Additive protective effects of donepezil and nicotine against salsolinol-induced cytotoxicity in SH-SY5Y cells. Neurotox Res. 2009 Oct;16(3):194-204.
• [9] Affinity profiles of various muscarinic antagonists for cloned human muscarinic acetylcholine receptor (mAChR) subtypes and mAChRs in rat heart and submandibular gland. Life Sci. 1999;64(25):2351-8.
• [10] 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: 7354).
• [11] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [12] Comparison of pharmacological effects of L- and DL-n-butyl-scopolamine in rat uterus. Yao Xue Xue Bao. 1994;29(1):24-7.
• [13] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [14] Comparison of the effects of metoclopramide and domperidone on HERG channels. Pharmacology. 2005 Apr;74(1):31-6. doi: 10.1159/000083234. Epub 2005 Jan 7.
• [15] Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005 Jan;16(1):54-8. doi: 10.1046/j.1540-8167.2005.04470.x.
• [16] Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds. Assay Drug Dev Technol. 2004 Oct;2(5):497-506. doi: 10.1089/adt.2004.2.497.
• [17] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
• [18] Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br J Pharmacol. 2008 Nov;155(6):957-66. doi: 10.1038/bjp.2008.325. Epub 2008 Aug 25.
• [19] Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy. Br J Pharmacol. 2006 Mar;147(6):642-52. doi: 10.1038/sj.bjp.0706508.
• [20] Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 1999 Mar;359(3):212-9. doi: 10.1007/pl00005344.
• [21] Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation. FEBS Lett. 2000 May 26;474(1):111-5. doi: 10.1016/s0014-5793(00)01586-6.