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

General Information of Drug (ID: DMO50U2)

• Drug Name: Naratriptan Drug Info
• Synonyms: Colatan; Naramig; Naratriptanum; Amerge (TN); Naramig (TN); Naratriptan (INN); Amerge, Naramig,Naratriptan; N-methyl-2-(3-(1-methylpiperiden-4-yl)indole-5-yl)ethanesulfonamide; N-methyl-2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonamide; N-methyl-2-[3-(1-methyl-4-piperidyl)-1H-indol-5-yl]-ethanesulfonamide

Indication

Disease Entry	ICD 11	Status	REF
Headache	8A80-8A84	Approved	[1]
Migraine	8A80	Approved	[2]
Migraine disorder		Approved	[1]

• Therapeutic Class: Vasoconstrictor Agents
• Cross-matching ID:
  PubChem CID: 4440
  ChEBI ID: CHEBI:7478
  CAS Number: CAS 121679-13-8
  TTD Drug ID: DMO50U2
  VARIDT Drug ID: DR01282
  INTEDE Drug ID: DR1131
  ACDINA Drug ID: D00457

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT 1B receptor (HTR1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[7]
Eletriptan	DMW649X	Migraine	8A80	Approved	[8]
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[8]
Frovatriptan	DM7RE8P	Migraine	8A80	Approved	[8]
Fluphenazine	DMIT8LX	Psychotic disorder	6A20-6A25	Approved	[8]
Prolixin decanoate	DMMJ1IS	Schizophrenia	6A20	Approved	[8]
Eltoprazine	DMW6C81	Attention deficit hyperactivity disorder	6A05.Z	Phase 3	[9]
NXN-188	DMMBAIH	Migraine	8A80	Phase 2	[10]
[N-methyl-3H(3)]AZ-10419369	DMSCV02	Mood disorder	6A60-6E23	Phase 1	[11]
Alniditan	DMFE3CT	Migraine	8A80	Discontinued in Phase 3	[12]

Drug(s) Transported By Organic cation transporter 1 (SLC22A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[13]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[14]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[16]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[17]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[18]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[19]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[20]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[21]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[22]

Drug(s) Metabolized By Monoamine oxidase type A (MAO-A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[23]
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[24]
Safinamide mesylate	DM0J2ZT	Parkinson disease	8A00.0	Approved	[25]
Almotriptan malate	DMFG5ST	N. A.	N. A.	Approved	[26]
SEROTONIN	DMOFCRY	Discovery agent	N.A.	Investigative	[27]
PHENETHYLAMINE	DMX0G4F	Discovery agent	N.A.	Investigative	[27]
Benzylamine	DMRM6ES	N. A.	N. A.	Investigative	[27]

Drug(s) Affected By Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (GNB3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[28]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[29]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[30]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[31]
Rosiglitazone	DMILWZR	Chronic kidney disease	GB61	Approved	[32]
Cytarabine	DMZD5QR	Acute lymphoblastic leukaemia	2A85	Approved	[33]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[34]
Nortriptyline	DM4KDYJ	Depression	6A70-6A7Z	Approved	[35]
Sibutramine	DMFJTDI	Obesity	5B81	Approved	[36]
Almogran	DM7I64Z	Migraine	8A80	Approved	[6]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 1B receptor (HTR1B)	TTK8CXU	5HT1B_HUMAN	Agonist	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Monoamine oxidase type A (MAO-A) Main DME	DERE4TU	AOFA_HUMAN	Substrate	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (GNB3)	OTA6HYBA	GBB3_HUMAN	Drug Response	[6]

References

• [1] Naratriptan FDA Label
• [2] 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: 45).
• [3] Triptans in pregnancy. Ther Drug Monit. 2008 Feb;30(1):5-9.
• [4] OCT1 mediates hepatic uptake of sumatriptan and loss-of-function OCT1 polymorphisms affect sumatriptan pharmacokinetics. Clin Pharmacol Ther. 2016 Jun;99(6):633-41.
• [5] Migraine pharmacotherapy with oral triptans: a rational approach to clinical management. Expert Opin Pharmacother. 2000 Mar;1(3):391-404.
• [6] G protein beta3 polymorphism and triptan response in cluster headache. Clin Pharmacol Ther. 2007 Oct;82(4):396-401. doi: 10.1038/sj.clpt.6100159. Epub 2007 Mar 14.
• [7] Two amino acid differences in the sixth transmembrane domain are partially responsible for the pharmacological differences between the 5-HT1D beta and 5-HT1E 5-hydroxytryptamine receptors. J Neurochem. 1996 Nov;67(5):2096-103.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
• [10] Company report (NeurAxon)
• [11] 5-HT1B and other related serotonergic proteins are altered in APPswe mutation. Neurosci Lett. 2015 May 6;594:137-43.
• [12] Agonistic properties of alniditan, sumatriptan and dihydroergotamine on human 5-HT1B and 5-HT1D receptors expressed in various mammalian cell lines. Br J Pharmacol. 1998 Apr;123(8):1655-65.
• [13] Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
• [14] Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family). J Pharmacol Exp Ther. 2006 Nov;319(2):879-86.
• [15] Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leuk Lymphoma. 2008 Apr;49(4):639-42.
• [16] Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57.
• [17] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [18] Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
• [19] Upregulation of histone acetylation reverses organic anion transporter 2 repression and enhances 5-fluorouracil sensitivity in hepatocellular carcinoma
• [20] Comparison of type I and type II organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5.
• [21] Organic cation transporters and their pharmacokinetic and pharmacodynamic consequences. Drug Metab Pharmacokinet. 2008;23(4):243-53.
• [22] Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
• [23] Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males: a case control study. J Neurooncol. 2019 Nov;145(2):287-294.
• [24] Med-psych drug-drug interactions update. Psychosomatics. 2002 May;43(3):245-7.
• [25] Solid-phase synthesis and insights into structure-activity relationships of safinamide analogues as potent and selective inhibitors of type B monoamine oxidase. J Med Chem. 2007 Oct 4;50(20):4909-16.
• [26] Clinical pharmacokinetics of almotriptan, a serotonin 5-HT(1B/1D) receptor agonist for the treatment of migraine. Clin Pharmacokinet. 2005;44(3):237-46.
• [27] Do monomeric vs dimeric forms of MAO-A make a difference? A direct comparison of the catalytic properties of rat and human MAO-A's. J Neural Transm (Vienna). 2007;114(6):721-4.
• [28] G-protein gene 825C>T polymorphism is associated with response to clozapine in Brazilian schizophrenics. Pharmacogenomics. 2008 Oct;9(10):1429-36. doi: 10.2217/14622416.9.10.1429.
• [29] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [30] 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.
• [31] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [32] Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity (Silver Spring). 2010 Jan;18(1):27-34. doi: 10.1038/oby.2009.208. Epub 2009 Jun 25.
• [33] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [34] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [35] Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein beta3 subunit as predictors of response to fluoxetine and nortriptyline. Int J Neuropsychopharmacol. 2003 Dec;6(4):339-46. doi: 10.1017/S1461145703003663.
• [36] Weight loss and body fat reduction under sibutramine therapy in obesity with the C825T polymorphism in the GNB3 gene. Pharmacogenet Genomics. 2009 Sep;19(9):730-3. doi: 10.1097/FPC.0b013e3283307cf1.