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

General Information of Drug (ID: DM0J2ZT)

• Drug Name: Safinamide mesylate Drug Info
• Synonyms: Safinamide mesylate; Safinamide mesilate; PNU-151774E; UNII-YS90V3DTX0; FCE-28073; NW-1015; Safinamide mesylate [USAN]; YS90V3DTX0; FCE-28073(R-isomer); Safinamide mesylate (USAN); safinamide methanesulfonate; PNU 151774E; Xadago (TN); NW 1015; AC1MI4YU; Safinamide mesilate (JAN)

Indication

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

• Cross-matching ID:
  PubChem CID: 3038502
  CAS Number: CAS 202825-46-5
  TTD Drug ID: DM0J2ZT
  INTEDE Drug ID: DR1456

Molecule-Related Drug Atlas

Drug(s) Targeting Monoamine oxidase type B (MAO-B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selegiline Hydrochloride	DM3VR1L	Parkinson disease	8A00.0	Approved	[4]
Phenelzine	DMHIDUE	Depression	6A70-6A7Z	Approved	[5]
Tranylcypromine	DMGB5RE	Major depressive disorder	6A70.3	Approved	[6]
Selegiline	DM6034S	Major depressive disorder	6A70.3	Approved	[7]
Rasagiline	DM3WKQ4	Parkinson disease	8A00.0	Approved	[8]
Sulphadoxine	DMZI2UF	Malaria	1F40-1F45	Approved	[9]
Pargyline	DMM0HR1	Hypertension	BA00-BA04	Approved	[10]
Indeloxazine	DMWO3N6	Dementia	6D80-6D86	Approved	[11]
Budipine	DMODHQI	Migraine	8A80	Approved	[12]
Safinamide	DM0YWJC	Parkinson disease	8A00.0	Approved	[13]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	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]
Naratriptan	DMO50U2	Headache	8A80-8A84	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]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[2]
Monoamine oxidase type A (MAO-A) Main DME	DERE4TU	AOFA_HUMAN	Substrate	[3]

References

• [1] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [2] Disposition and metabolism of safinamide, a novel drug for Parkinson's disease, in healthy male volunteers. Pharmacology. 2013;92(3-4):207-16.
• [3] 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.
• [4] Emerging drugs for Parkinson's disease. Expert Opin Emerg Drugs. 2006 Sep;11(3):403-17.
• [5] Limitation of adipose tissue enlargement in rats chronically treated with semicarbazide-sensitive amine oxidase and monoamine oxidase inhibitors. Pharmacol Res. 2008 Jun;57(6):426-34.
• [6] Tranylcypromine: new perspectives on an "old" drug. Eur Arch Psychiatry Clin Neurosci. 2006 Aug;256(5):268-73.
• [7] 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. (Target id: 2490).
• [8] Glyceraldehyde-3-phosphate dehydrogenase-monoamine oxidase B-mediated cell death-induced by ethanol is prevented by rasagiline and 1-R-aminoindan. Neurotox Res. 2009 Aug;16(2):148-59.
• [9] Novel monoamine oxidase inhibitors, 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives, and their differential reversibility. Jpn J Pharmacol. 2002 Feb;88(2):174-82.
• [10] Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells. Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H821-8.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [12] Multiple mechanisms of action: the pharmacological profile of budipine. J Neural Transm Suppl. 1999;56:83-105.
• [13] Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007 Sep;12(3):407-22.
• [14] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [15] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [16] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [17] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [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] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [22] 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.
• [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] Migraine pharmacotherapy with oral triptans: a rational approach to clinical management. Expert Opin Pharmacother. 2000 Mar;1(3):391-404.
• [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.