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

General Information of Drug (ID: DM5QWEL)

• Drug Name: Guanabenz Drug Info
• Synonyms: GBZ; Guanabenzo; Guanabenzum; Wytensin; Guanabenz acetate; Guanabenz monoacetate; Wy 8678; Wy 8678 base; BR-750; Guanabenz [USAN:INN]; Guanabenz(USAN); Guanabenzo [INN-Spanish]; Guanabenzum [INN-Latin]; Wy-8678; Wytensin (TN); Guanabenz (USAN/INN); [(2,6-Dichlorobenzylidene)amino]guanidine; N-((2,6-Dichlorobenzylidene)amino)guanidine; Guanidine, ((2,6-dichlorobenzylidene)amino)-(8CI); N-(2,6-Dichlorobenzylidene)-N'-amidinohydrazine; ((2,6-Dichlorobenzylidene)amino)guanidine; 2,6-Dichlorobenzylideneaminoguanidine;2-((2,6-Dichlorophenyl)methylene)-hydrazinecarboximidamide; 2-[(E)-(2,6-dichlorophenyl)methylideneamino]guanidine

Indication

Disease Entry	ICD 11	Status	REF
High blood pressure	BA00	Approved	[1]

• Therapeutic Class: Sympatholytics
• Cross-matching ID:
  PubChem CID: 5702063
  ChEBI ID: CHEBI:5553
  CAS Number: CAS 60329-03-5
  TTD Drug ID: DM5QWEL
  VARIDT Drug ID: DR01410
  INTEDE Drug ID: DR0794

Molecule-Related Drug Atlas

Drug(s) Targeting Adrenergic receptor Alpha-2 (ADRA2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[5]
Meperidine	DMX4GND	Pain	MG30-MG3Z	Approved	[6]
Lofexidine	DM1WXA6	Heroin and opiate withdrawal	6C43	Approved	[7]
Sodium chloride	DMM3950	Skin burns	ME65.0	Approved	[5]
Guanfacine extended release	DMB1CZ8	Attention deficit hyperactivity disorder	6A05.Z	Approved	[8]
Dexmedetomidine	DM93L4X	Irritability	MB24	Approved	[9]
Yohimbine	DMJCP1Y	Erectile dysfunction	HA01.1	Approved	[10]
Tizanidine	DMR2IQ4	Spasm	MB47.3	Approved	[11]
Oxymetazoline	DM8ZXT6	Arrhythmia	BC9Z	Approved	[12]
Brimonidine	DMQLT4N	Ocular hypertension	9C61.01	Approved	[13]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[14]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[16]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[17]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[16]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[16]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[18]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[21]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[22]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[23]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[24]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[25]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[27]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[28]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[29]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor Alpha-2 (ADRA2)	TTQ8AFT	NOUNIPROTAC	Agonist	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2) Main DME	DEJGDUW	CP1A2_HUMAN	Substrate	[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: 5443).
• [2] Centrally acting sympathetic inhibitors for therapy of patients with hypertension. Nippon Rinsho. 1997 Aug;55(8):2081-5.
• [3] A novel screening strategy to identify ABCB1 substrates and inhibitors. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jan;379(1):11-26.
• [4] Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218.
• [5] Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats. Pharmacol Biochem Behav. 2000 Nov;67(3):397-403.
• [6] Meperidine, remifentanil and tramadol but not sufentanil interact with alpha(2)-adrenoceptors in alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptor ... Eur J Pharmacol. 2008 Mar 17;582(1-3):70-7.
• [7] Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis. Am J DrugAlcohol Abuse. 2008;34(5):611-6.
• [8] Emerging drugs for attention-deficit/hyperactivity disorder. Expert Opin Emerg Drugs. 2007 Sep;12(3):423-34.
• [9] Dexmedetomidine in intensive care unit: a study of hemodynamic changes. Middle East J Anesthesiol. 2002 Oct;16(6):587-95.
• [10] Acute neurotoxicity after yohimbine ingestion by a body builder. Clin Toxicol (Phila). 2009 Sep;47(8):827-9.
• [11] Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997 Mar;53(3):435-52.
• [12] Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries. Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2049-55.
• [13] Increased alpha2-adrenergic constriction of isolated arterioles in diffuse scleroderma. Arthritis Rheum. 2000 Aug;43(8):1886-90.
• [14] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [15] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [16] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [17] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [18] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [19] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [20] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [21] 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.
• [22] 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.
• [23] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [24] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [25] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [26] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [27] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [28] 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.
• [29] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [30] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.