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

General Information of Drug (ID: DMVHJLX)

• Drug Name: Perospirone Drug Info
• Synonyms: Lullan; SM-9018

Indication

Disease Entry	ICD 11	Status	REF
Psychotic disorder	6A20-6A25	Approved	[1]

• Cross-matching ID:
  PubChem CID: 115368
  ChEBI ID: CHEBI:94777
  CAS Number: CAS 150915-41-6
  TTD Drug ID: DMVHJLX
  INTEDE Drug ID: DR1263

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT 2 receptor (5HT2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mianserin	DMVKA4O	Depression	6A70-6A7Z	Approved	[5]
Cyclobenzaprine	DM1YBRM	Depression	6A70-6A7Z	Approved	[6]
Ketanserin	DMVLMW6	Hypertension	BA00-BA04	Approved	[7]
Bis(olanzapine) pamoate monohydrate	DME76AP	Psychotic disorder	6A20-6A25	Phase 3	[8]
FKB01MD	DM2O7NM	N. A.	N. A.	Phase 2	[9]
Nexopamil	DML5S71	Hypertension	BA00-BA04	Phase 2	[10]
TGWOOAA	DMI57ZA	Generalized anxiety disorder	6B00	Phase 2	[11]
TGOF02N	DMQ6ANE	Schizophrenia	6A20	Phase 2	[12]
AMAP-102	DM7CD8Z	Arthritis	FA20	Phase 1	[13]
Heterocyclic-tetracyclic tetrahydrofuran derivative 1	DMNJVR6	N. A.	N. A.	Patented	[14]

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[20]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[21]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[22]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[23]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[24]

Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[25]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[26]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[27]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[28]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[29]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[30]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[26]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[31]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[32]

Drug(s) Affected By 5-hydroxytryptamine receptor 1A (HTR1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[33]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[33]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[34]
Methamphetamine	DMPM4SK	Anxiety		Approved	[35]
Olanzapine	DMPFN6Y	Bipolar depression		Approved	[4]
Etoperidone	DMR7U8F	N. A.	N. A.	Phase 4	[33]
phorbol 12-myristate 13-acetate	DMJWD62	Acute myeloid leukaemia	2A60	Phase 2	[36]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[37]
DU 125530	DM63UA9	Mood disorder	6A60-6E23	Discontinued in Phase 2	[38]
THAPSIGARGIN	DMDMQIE	N. A.	N. A.	Preclinical	[36]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 2 receptor (5HT2R)	TTYSN63	NOUNIPROTAC	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[3]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
5-hydroxytryptamine receptor 1A (HTR1A)	OT38K9MK	5HT1A_HUMAN	Drug Response	[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: 7556).
• [2] Pharmacological effects of zotepine and other antipsychotics on the central 5-HT2 receptors. Pharmacopsychiatry. 1993 Mar;26(2):53-8.
• [3] Steady-state pharmacokinetics of a new antipsychotic agent perospirone and its active metabolite, and its relationship with prolactin response. Ther Drug Monit. 2004 Aug;26(4):361-5.
• [4] Serotonin-1A receptor gene polymorphism and the ability of antipsychotic drugs to improve attention in schizophrenia. Adv Ther. 2010 May;27(5):307-13. doi: 10.1007/s12325-010-0035-4. Epub 2010 Jun 8.
• [5] 5-HT reuptake and 5-HT2 receptors modulate capsaicin-evoked hypothermia in rats. Neurosci Lett. 2008 Jan 17;430(3):191-6.
• [6] Torticollis under Cyclobenzaprine. Pharmacology. 2009 Jul 8;84(2):91-92.
• [7] Nordexfenfluramine causes more severe pulmonary vasoconstriction than dexfenfluramine. Am J Physiol Lung Cell Mol Physiol. 2004 Mar;286(3):L531-8.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Inhibition by the combined Ca2+ and 5-HT2 receptor antagonist nexopamil (LU 49938) of intracoronary thrombus formation in a canine model of arterial stenosis and intimal damage. J Cardiovasc Pharmacol. 1993 Nov;22(5):687-94.
• [11] Clinical pipeline report, company report or official report of Fabre-Kramer Pharmaceuticals.
• [12] Clinical pipeline report, company report or official report of Fabre-Kramer Pharmaceuticals.
• [13] Clinical pipeline report, company report or official report of Anamar.
• [14] Novel serotonin receptor 2 (5-HT2R) agonists and antagonists: a patent review (2004-2014).Expert Opin Ther Pat. 2016;26(1):89-106.
• [15] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [16] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [17] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [18] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [19] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [20] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [21] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [22] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [23] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [24] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
• [25] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [26] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [27] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [28] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [29] Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
• [30] Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
• [31] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [32] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [33] Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. doi: 10.1007/BF02244985.
• [34] Response to fluoxetine and serotonin 1A receptor (C-1019G) polymorphism in Taiwan Chinese major depressive disorder. Pharmacogenomics J. 2006 Jan-Feb;6(1):27-33. doi: 10.1038/sj.tpj.6500340.
• [35] Serotonin 1A receptor gene is associated with Japanese methamphetamine-induced psychosis patients. Neuropharmacology. 2010 Feb;58(2):452-6. doi: 10.1016/j.neuropharm.2009.09.006. Epub 2009 Sep 10.
• [36] Mechanisms of regulation of agonist efficacy at the 5-HT(1A) receptor by phospholipid-derived signaling components. J Pharmacol Exp Ther. 2001 Jun;297(3):1025-35.
• [37] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [38] 5-Hydroxytryptamine1A receptor occupancy by novel full antagonist 2-[4-[4-(7-chloro-2,3-dihydro-1,4-benzdioxyn-5-yl)-1-piperazinyl]butyl]-1,2-benzisothiazol-3-(2H)-one-1,1-dioxide: a[11C][O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) positron emission tomography study in humans. J Pharmacol Exp Ther. 2002 Jun;301(3):1144-50.