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

General Information of Drug (ID: DMKNUP3)

• Drug Name: norfluoxetine Drug Info
• Synonyms: Norfluoxetine; Desmethylfluoxetine; Norfluoxetin; 56161-73-0; 83891-03-6; 3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine; WIQRCHMSJFFONW-UHFFFAOYSA-N; gamma-(4-(Trifluoromethyl)phenoxy)benzenepropanamine; norfluoxetine hcl; 3-Phenyl-3-(4-trifluoromethyl-phenoxy)-propylamine; 3-phenyl-3-(4-(trifluoromethyl)phenoxy)propan-1-amine; Benzenepropanamine, gamma-(4-(trifluoromethyl)phenoxy)-; benzenepropanamine, gamma-[4-(trifluoromethyl)phenoxy]-; ( inverted exclamation markA)-

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 4541
  ChEBI ID: CHEMBL1494
  CAS Number: CAS 83891-03-6
  TTD Drug ID: DMKNUP3

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT 2B receptor (HTR2B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[6]
Triflupromazine	DMKFQJP	Nausea	MD90	Approved	[7]
Minaprine	DM0EP7M	Depression	6A70-6A7Z	Approved	[8]
SPN-812	DMTV7XH	Attention deficit hyperactivity disorder	6A05.Z	Phase 4	[9]
Vabicaserin	DM9GZW6	Psychotic disorder	6A20-6A25	Phase 2	[10]
PRX-08066	DMR7H2V	Pulmonary arterial hypertension	BB01.0	Phase 2	[11]
Pyrimidine derivative 29	DMVOYJ8	N. A.	N. A.	Patented	[12]
Pyrimidine derivative 26	DM90WKN	N. A.	N. A.	Patented	[12]
Pyrimidine derivative 23	DM5MLQU	N. A.	N. A.	Patented	[12]
Pyrimidine derivative 25	DM51MFS	N. A.	N. A.	Patented	[12]

Drug(s) Targeting 5-HT 2A receptor (HTR2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[6]
ZOTEPINE	DMF3VXA	Anxiety disorder	6B00-6B0Z	Approved	[13]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[14]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[15]
Lurasidone hydrochloride	DMCVPXO	Schizophrenia	6A20	Approved	[16]
Aniracetam	DMOIFW0	Cerebrovascular ischaemia	8B1Z	Approved	[17]
lumateperone tosylate	DMQ8HOJ	Schizophrenia	6A20	Approved	[18]
Sarpogrelate	DMGLP6S	Diabetic complication	5A2Y	Approved	[19]
Pimavanserin	DMR7IVC	Parkinson disease	8A00.0	Approved	[20]
Zicronapine	DMP8ESD	Schizophrenia	6A20	Phase 3	[21]

Drug(s) Targeting Voltage-gated potassium channel Kv3.1 (KCNC1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[22]

Drug(s) Targeting 5-HT 2C receptor (HTR2C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[6]
Lorcaserin	DMG6OYJ	Obesity	5B81	Approved	[23]
Tramadol	DMRQD04	Osteoarthritis	FA00-FA05	Approved	[24]
Mirtazapine	DML53ZJ	Depression	6A70-6A7Z	Approved	[4]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[25]
Methysergide	DM1EF73	Migraine	8A80	Approved	[26]
Eltoprazine	DMW6C81	Attention deficit hyperactivity disorder	6A05.Z	Phase 3	[27]
M100907	DM7ZFBA	Sleep-wake disorder	7A00-7B2Z	Phase 3	[28]
SR46349B	DM1ODMR	Primary insomnia	7A00	Phase 3	[29]
Vabicaserin	DM9GZW6	Psychotic disorder	6A20-6A25	Phase 2	[10]

Drug(s) Affected By 5-hydroxytryptamine receptor 2C (HTR2C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[4]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[4]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[4]
Fluphenazine	DMIT8LX	Psychotic disorder	6A20-6A25	Approved	[30]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[31]
Nortriptyline	DM4KDYJ	Depression	6A70-6A7Z	Approved	[32]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[33]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[34]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[35]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[36]

Drug(s) Affected By Choriogonadotropin subunit beta variant 2 (CGB2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[37]
Permethrin	DMZ0Q1G	Pediculus capitis infestation	1G00.0	Approved	[38]
(+)-JQ1	DM1CZSJ	Testicular cancer	2C80	Phase 1	[39]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[40]
Forskolin	DM6ITNG	Solid tumour/cancer	2A00-2F9Z	Investigative	[5]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Antagonist	[2]
5-HT 2B receptor (HTR2B)	TT0K1SC	5HT2B_HUMAN	Antagonist	[2]
5-HT 2C receptor (HTR2C)	TTWJBZ5	5HT2C_HUMAN	Antagonist	[2]
Voltage-gated potassium channel Kv3.1 (KCNC1)	TTVUWHQ	KCNC1_HUMAN	Inhibitor (gating inhibitor)	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
5-hydroxytryptamine receptor 2C (HTR2C)	OT6H8DE0	5HT2C_HUMAN	Protein Interaction/Cellular Processes	[4]
Choriogonadotropin subunit beta variant 2 (CGB2)	OTZJW4TH	CGB2_HUMAN	Gene/Protein Processing	[5]

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: 208).
• [2] Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. 2000 Dec 5;102(23):2836-41.
• [3] Effects of norfluoxetine, the major metabolite of fluoxetine, on the cloned neuronal potassium channel Kv3.1. Neuropharmacology. 2001 Sep;41(4):443-53.
• [4] Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulatio... Mol Pharmacol. 2008 Mar;73(3):748-57.
• [5] Effects of selective serotonin-reuptake inhibitors (SSRIs) on human villous trophoblasts syncytialization. Toxicol Appl Pharmacol. 2018 Jun 15;349:8-20. doi: 10.1016/j.taap.2018.04.018. Epub 2018 Apr 19.
• [6] Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23.
• [7] Some properties of 5-hydroxytryptamine receptors in the hindquarters of the rat. Br J Pharmacol. 1979 Sep;67(1):79-85.
• [8] Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
• [9] New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300.
• [10] Prediction of Efficacy of Vabicaserin, a 5-HT2C Agonist, for the Treatment of Schizophrenia Using a Quantitative Systems Pharmacology Model.CPT Pharmacometrics Syst Pharmacol.2014 Apr 23;3:e111.
• [11] Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
• [12] Novel serotonin receptor 2 (5-HT2R) agonists and antagonists: a patent review (2004-2014).Expert Opin Ther Pat. 2016;26(1):89-106.
• [13] Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
• [14] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [15] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [16] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [17] Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism. Eur J Pharmacol. 2001 May 18;420(1):33-43.
• [18] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [19] Beneficial effects of sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, supplemented with pioglitazone on diabetic model mice. Endocr Res. 2009;34(1-2):18-30.
• [20] Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2mg/day, but does not enhance efficacy of haloperidol, 2mg/day: comparison with reference dose risperidone, 6mg/day.Schizophr Res.2012 Nov;141(2-3):144-52.
• [21] Clinical pipeline report, company report or official report of Lundbeck.
• [22] Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol. 1994 Jun;45(6):1227-34.
• [23] Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.
• [24] The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in Xenopus oocytes. Anesth Analg. 2004 May;98(5):1401-6, table of contents.
• [25] Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005 Sep-Oct;60(5):441-60.
• [26] Spinal serotonin receptor activation modulates the exercise ventilatory response with increased dead space in goats. Respir Physiol Neurobiol. 2008 May 31;161(3):230-8.
• [27] Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
• [28] Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists ... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3708-12.
• [29] SR46349-B, a 5-HT(2A/2C) receptor antagonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Neuropsychopharmacology. 2002 Sep;27(3):430-41.
• [30] Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs. Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11927-32. doi: 10.1073/pnas.0609752104. Epub 2007 Jul 2.
• [31] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [32] Downregulation of serotonin receptor subtypes by nortriptyline and adinazolam in major depressive disorder: neuroendocrine and platelet markers. Clin Neuropharmacol. 1993;16 Suppl 3:S19-31.
• [33] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [34] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [35] 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.
• [36] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [37] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [38] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [39] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [40] 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.