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

General Information of Drug (ID: DM42GP9)

• Drug Name: Bicifadine Drug Info
• Synonyms: BICIFADINE; 71195-57-8; 1-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane; 1-(p-Tolyl)-3-azabicyclo[3.1.0]hexane; 1-p-tolyl-3-azabicyclo[3.1.0]hexane; 5-(4-methylphenyl)-3-azabicyclo[3.1.0]hexane; 3-Azabicyclo[3.1.0]hexane, 1-(4-methylphenyl)-; CL-220075; PubChem18323; AC1L2J2O; SCHEMBL38793; AZA001; CHEMBL511099; OFYVIGTWSQPCLF-UHFFFAOYSA-N; NIH-9542; MCV-4147; BDBM50417944; AKOS006271730; DOV-220075; AN-3206; DB04889; KB-13207; 5-(p-tolyl)-3-azabicyclo[3.1.0]hexane; AM20041063; FT-0718156; 1-(p-tolyl)-3-azabicyclo[3.1.0]-hexane

Indication

Disease Entry	ICD 11	Status	REF
Chronic low back pain	MG30.02	Phase 3	[1]
Neuropathic pain	8E43.0	Phase 3	[1]

• Therapeutic Class: Analgesics
• Cross-matching ID:
  PubChem CID: 47953
  CAS Number: CAS 71195-57-8
  TTD Drug ID: DM42GP9
  VARIDT Drug ID: DR01143
  INTEDE Drug ID: DR0211

Molecule-Related Drug Atlas

Drug(s) Targeting Norepinephrine transporter (NET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[4]
Amitriptyline	DMK7F9S	Depression	6A70-6A7Z	Approved	[5]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[6]
Desipramine	DMT2FDC	Attention deficit hyperactivity disorder	6A05.Z	Approved	[4]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[7]
Bupropion	DM5PCS7	Depression	6A70-6A7Z	Approved	[8]
Tapentadol hydrochloride	DMXLSH3	Acute pain	MG31	Approved	[9]
Venlafaxine	DMR6QH0	Anxiety disorder	6B00-6B0Z	Approved	[8]
Trimipramine	DM1SC8M	Major depressive disorder	6A70.3	Approved	[10]
Duloxetine	DM9BI7M	Depression	6A70-6A7Z	Approved	[11]

Drug(s) Targeting Serotonin transporter (SERT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[4]
Amitriptyline	DMK7F9S	Depression	6A70-6A7Z	Approved	[5]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[12]
Vortioxetine	DM6F1PU	Major depressive disorder	6A70.3	Approved	[13]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[14]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[7]
Bupropion	DM5PCS7	Depression	6A70-6A7Z	Approved	[8]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[12]
Nortriptyline	DM4KDYJ	Depression	6A70-6A7Z	Approved	[12]
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[12]

Drug(s) Metabolized By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[15]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[21]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[22]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[23]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[24]

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	[25]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[26]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[27]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[28]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[29]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[30]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[31]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[32]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[33]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Modulator	[2]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	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 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[3]

References

• [1] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [2] Preclinical Evaluation of the Abuse Potential of the Analgesic Bicifadine
• [3] In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human. Drug Metab Dispos. 2007 Dec;35(12):2232-41.
• [4] Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice. Psychopharmacology (Berl). 2009 Sep;206(1):97-107.
• [5] Treatment of comorbid pain with serotonin norepinephrine reuptake inhibitors. CNS Spectr. 2008 Jul;13(7 Suppl 11):22-6.
• [6] Invivo antioxidant status: a putative target of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):220-8.
• [7] Differential involvement of the norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion. Pharmacol Biochem Behav. 2009 Jul;93(1):75-81.
• [8] Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.
• [9] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [10] Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade. Eur Neuropsychopharmacol. 2006 Oct;16(7):481-90.
• [11] Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [13] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [14] Psychopharmacological treatment of dermatological patients--when simply talking does not help. J Dtsch Dermatol Ges. 2007 Dec;5(12):1101-6.
• [15] 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.
• [16] Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
• [17] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [18] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [19] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [20] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [21] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [22] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [23] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [24] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
• [25] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [26] 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.
• [27] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [32] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [33] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [34] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.