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

General Information of Drug (ID: DMV74ZH)

• Drug Name: Pizotyline Drug Info
• Synonyms: Pizotifen; PIZOTYLINE; 15574-96-6; Sandomigran; Litec; Sandomygran; Pizotifenum; Pizotifeno; Polomigran; Pizotifene; BC-105; BC 105; Pizotyline [USAN]; Pizotifan; Pizotifene [INN-French]; Pizotifenum [INN-Latin]; Pizotifeno [INN-Spanish]; UNII-0BY8440V3N; EINECS 239-632-9; BRN 0753534; C19H21NS; CHEBI:50212; FIADGNVRKBPQEU-UHFFFAOYSA-N; Pizotifen (INN); Pizotifen [INN]; 0BY8440V3N; Pizotyline (USAN); 4-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-ylidene)-1-methylpiperidine

Indication

Disease Entry	ICD 11	Status	REF
Headache	8A80-8A84	Approved	[1]

• Cross-matching ID:
  PubChem CID: 27400
  ChEBI ID: CHEBI:50212
  CAS Number: CAS 15574-96-6
  TTD Drug ID: DMV74ZH
  INTEDE Drug ID: DR1308

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT receptor (5HTR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[5]
Paliperidone	DM7NPJS	Psychotic disorder	6A20-6A25	Approved	[2]
Ramosetron	DMH7GN8	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[5]
Tandospirone	DMPHWU6	Anxiety disorder	6B00-6B0Z	Approved	[5]
Nafronyl	DMVMQ1L	Cerebrovascular ischaemia	8B1Z	Approved	[2]
ITI-007	DMUQ1DO	Depression	6A70-6A7Z	Phase 3	[6]
Fenfluramine	DM0762O	Dravet syndrome	8A61.11	Phase 3	[7]
MIN-117	DMSLIW6	Major depressive disorder	6A70.3	Phase 2	[6]
Lu-AA34893	DM2ZUXK	Anxiety disorder	6B00-6B0Z	Phase 2	[8]
SEP--4199	DMA12HB	Bipolar disorder	6A60	Phase 2	[9]

Drug(s) Metabolized By UDP-glucuronosyltransferase 2B10 (UGT2B10)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Desloratadine	DM56YN7	Allergic rhinitis	CA08.0	Approved	[10]
Cotinine	DMCEZ1B	Insecticide	N.A.	Approved	[11]

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	[12]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[13]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[14]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[15]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[15]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[16]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[17]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[18]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[19]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[15]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT receptor (5HTR)	TT85JO3	NOUNIPROTAC	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 2B10 (UGT2B10) Main DME	DEI8NGH	UDB10_HUMAN	Substrate	[3]

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	[4]

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: 93).
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Human UDP-glucuronosyltransferase (UGT) 2B10 in drug N-glucuronidation: substrate screening and comparison with UGT1A3 and UGT1A4. Drug Metab Dispos. 2013 Jul;41(7):1389-97.
• [4] 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.
• [5] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Pharmacotherapy for obesity. Drugs. 2005;65(10):1391-418.
• [8] Encyclopedia of Psychopharmacology. Ian Stolerman. 2010. Page(105).
• [9] ClinicalTrials.gov (NCT03543410) A Clinical Study to Test the Effectiveness of an Investigational Drug to Treat People That Have Major Depressive Episodes When They Have Bipolar 1 Depression. U.S. National Institutes of Health.
• [10] Further characterization of the metabolism of desloratadine and its cytochrome P450 and UDP-glucuronosyltransferase inhibition potential: identification of desloratadine as a relatively selective UGT2B10 inhibitor. Drug Metab Dispos. 2015 Sep;43(9):1294-302.
• [11] Human UDP-glucuronosyltransferase (UGT) 2B10: validation of cotinine as a selective probe substrate, inhibition by UGT enzyme-selective inhibitors and antidepressant and antipsychotic drugs, and structural determinants of enzyme inhibition. Drug Metab Dispos. 2016 Mar;44(3):378-88.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.