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

General Information of Drug (ID: DM0JE6N)

• Drug Name: Metixene Drug Info
• Synonyms: Atosil; Contalyl; Dalpan; METHIXENE; Methixart; Methixen; Methyloxan; Metisene; Metixeno; Metixenum; Raunana; Tremaril;Tremarit; Tremonil; Tremoquil; Trest; Methixen [German]; Methixene hydrochloride; Metisene [DCIT]; Metixene hydrochloride; Tremaril hydrochloride; Metixene (INN); Metixene (TN); Metixene [INN:BAN]; Metixeno [INN-Spanish]; Metixenum [INN-Latin]; Methixene (*hydrochloride*); Metixene (*hydrochloride*); Tremonil (*hydrochloride*); 1-Methyl-3-(9H-thioxanthen-9-yl-methyl)piperidine; 1-Methyl-3-(9H-thioxanthen-9-ylmethyl)piperidine; 1-Methyl-3-(thioxanthen-9-ylmethyl) piperidine; 1-Methyl-3-(thioxanthen-9-ylmethyl)-1-piperidine; 1-methyl-3-(thioxanthen-9-ylmethyl)-piperidine hydrochloride; 60 SJ 1977; 60 SJ 1977 (*hydrochloride*); 9-(1'-Methylpiperidine-3'-methyl)thioxanthene

Indication

Disease Entry	ICD 11	Status	REF
Parkinson disease	8A00.0	Approved	[1]

• Therapeutic Class: Antiparkinson Agents
• Cross-matching ID:
  PubChem CID: 4167
  ChEBI ID: CHEBI:51024
  CAS Number: CAS 4969-02-2
  TTD Drug ID: DM0JE6N

Molecule-Related Drug Atlas

Drug(s) Targeting Muscarinic acetylcholine receptor M1 (CHRM1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[4]
Fesoterodine fumarate	DM13495	Overactive bladder	GC50.0	Approved	[5]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[6]
Clidinium	DMUMQZ0	Abdominal stomach pain	DD91.4	Approved	[7]
Trihexyphenidyl	DMB19L8	Dystonia	8A02	Approved	[8]
Oxyphenonium	DMMQHOZ	Visceral spasms	MD81.4	Approved	[9]
Benztropine	DMGZOVN	Parkinson disease	8A00.0	Approved	[10]
Glycopyrrolate	DM2M3ZA	Anaesthesia	9A78.6	Approved	[11]
Pirenzepine	DMP6M1N	Peptic ulcer	DA61	Approved	[12]
Cycrimine	DM8C43Q	Parkinson disease	8A00.0	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 M1 (CHRM1)	TTZ9SOR	ACM1_HUMAN	Modulator	[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] 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: 7232).
• [2] Roles of the M1 muscarinic acetylcholine receptor subtype in the regulation of basal ganglia function and implications for the treatment of Parkinson's disease.J Pharmacol Exp Ther.2012 Mar;340(3):595-603.
• [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] 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.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder. J Urol. 2004 Nov;172(5 Pt 1):2059-64.
• [7] Accidental acute clidinium toxicity. Emerg Med J. 2009 Jun;26(6):460.
• [8] The role of M1 muscarinic cholinergic receptors in the discriminative stimulus properties of N-desmethylclozapine and the atypical antipsychotic dr... Psychopharmacology (Berl). 2009 Apr;203(2):295-301.
• [9] Ultraviolet spectroscopic estimation of microenvironments and bitter tastes of oxyphenonium bromide in cyclodextrin solutions. J Pharm Sci. 1999 Aug;88(8):759-62.
• [10] Formulation and biopharmaceutical evaluation of transdermal patch containing benztropine. Int J Pharm. 2008 Jun 5;357(1-2):55-60.
• [11] Autonomic cardiovascular control during a novel pharmacologic alternative to ganglionic blockade. Clin Pharmacol Ther. 2008 May;83(5):692-701.
• [12] Negative crosstalk between M1 and M2 muscarinic autoreceptors involves endogenous adenosine activating A1 receptors at the rat motor endplate. Neurosci Lett. 2009 Aug 14;459(3):127-31.
• [13] Capillary gas chromatography of trihexyphenidyl, procyclidine and cycrimine in biological fluids. J Chromatogr. 1989 Sep 29;494:135-42.
• [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.