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

General Information of Drug (ID: DMZIXU9)

Drug Name

Dihydralazine Drug Info

Synonyms

Dihydralazine sulfate; 7327-87-9; Dihydralazine sulphate; 1,4-Dihydrazinophthalazine sulfate; Depressan; Hydralazine sulfate; Ophthazin Sulfate; UNII-1C2B1W91NK; CCRIS 5386; Sulfate de dihydralazine [French]; 1,4-Dihydrazinylphthalazine Sulfate; EINECS 230-808-0; 1C2B1W91NK; Phthalazine, 1,4-dihydrazino-, sulfate (1:1); 1,4-Dihydrazinophthalazine hydrogen sulfate; W-104459; Sulfate de dihydralazine; 1,4-dihydrazinophthalazine sulfate(1:1); Dihydralazinsulfat; C8H10N6.H2O4S; Nepresol (TN); Dihydralazine Sulfate,(S); AC1Q6XE2

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[1]

Cross-matching ID

PubChem CID: 10230
ChEBI ID: CHEBI:134841
CAS Number: CAS 484-23-1
TTD Drug ID: DMZIXU9
INTEDE Drug ID: DR0499

Molecule-Related Drug Atlas

Molecule Type:

DME

DOT

Drug Status:

Approved Drug(s)

Download the Complete Related Drug List

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	[7]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[8]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[9]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[10]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[11]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[13]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[8]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[15]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[16]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[17]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[18]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[19]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[20]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[21]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[13]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[22]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[23]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[24]
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[35]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[35]
Etoricoxib	DM6A4NW	Rheumatoid arthritis	FA20	Approved	[35]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[36]
Hesperetin	DMKER83	High blood cholesterol level	5C80.00	Approved	[37]
Stiripentol	DMMSDOY	Dravet syndrome	8A61.11	Approved	[38]
Nifedipine	DMSVOZT	Angina pectoris	BA40	Approved	[39]
Zileuton	DMVRIC2	Allergic asthma	CA23.0	Approved	[40]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[41]
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[5]
------------------------------------------------------------------------------------


⏷ Show the Full List of 20 Drug(s)

Drug(s) Metabolized By RNA cytidine acetyltransferase (hALP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[25]
Caffeine	DMKBJWP	Allergic rhinitis	CA08.0	Approved	[26]
Procainamide	DMNMXR8	Ventricular arrhythmias	BC71	Approved	[27]
Sulfamethoxazole	DMB08GE	Acute otitis media	AB00	Approved	[28]
Sulfadiazine	DMTW3R8	Rheumatic fever	1B40-1B42	Approved	[29]
Tobramycin	DMUI0CH	Bacteremia	1A73	Approved	[30]
Mesalazine	DMOL5IU	Diverticulitis		Approved	[31]
Allopurinol	DMLPAOB	Gout	FA25	Approved	[32]
Netilmicin	DMRD1QK	Bacterial infection	1A00-1C4Z	Approved	[33]
Clonazepam	DMTO13J	Absence epilepsy		Approved	[34]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By Renin (REN)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[42]
Acebutolol	DM0TI4U	Hypertension	BA00-BA04	Approved	[43]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[44]
Reboxetine	DM26PRD	Depression	6A70-6A7Z	Approved	[45]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[46]
Ramipril	DM2R68E	Acute heart failure	BD10-BD13	Approved	[47]
Rhucin	DM3ADGP	Erectile dysfunction	HA01.1	Approved	[48]
Naloxone	DM3FXMA	Narcotic depression	6A7Z	Approved	[49]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[50]
Chlorthalidone	DM4DMBT	Edema	MG29	Approved	[51]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[2]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[3]
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Substrate	[4]

------------------------------------------------------------------------------------

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Drug Response	[5]
Renin (REN)	OT52GZR2	RENI_HUMAN	Gene/Protein Processing	[6]

------------------------------------------------------------------------------------

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2	Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet. 2005;44(3):279-304.
3	Mechanism-based inactivation of cytochrome P450s 1A2 and 3A4 by dihydralazine in human liver microsomes. Chem Res Toxicol. 1999 Oct;12(10):1028-32.
4	The influence of the acetylator phenotype for the clinical use of dihydralazine. Int J Clin Pharmacol Ther Toxicol. 1985 Apr;23 Suppl 1:S74-8.
5	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
6	Additive effects of dihydralazine during enflurane or isoflurane hypotensive anaesthesia for spinal fusion. Can J Anaesth. 1988 May;35(3 ( Pt 1)):242-8. doi: 10.1007/BF03010617.
7	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.
8	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
9	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.
10	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
11	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.
12	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.
13	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
14	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.
15	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.
16	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.
17	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.
18	Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
19	Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
20	PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
21	The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
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	Arylamine N-acetyltransferase in human red blood cells. Biochem Pharmacol. 1992 Sep 25;44(6):1099-104.
26	A population and family study of N-acetyltransferase using caffeine urinary metabolites. Clin Pharmacol Ther. 1993 Aug;54(2):134-41.
27	Effect of H2-receptor antagonists on rat liver cytosolic acetyl CoA:arylamine N-acetyltransferase activity. Drug Metab Dispos. 1992 Jan-Feb;20(1):74-8.
28	Crystallization and preliminary X-ray characterization of arylamine N-acetyltransferase C (BanatC) from Bacillus anthracis. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Oct 1;63(Pt 10):862-4.
29	Identification of cytochrome P450 and arylamine N-acetyltransferase isoforms involved in sulfadiazine metabolism. Drug Metab Dispos. 2005 Jul;33(7):969-76.
30	Genetic analysis of bacterial acetyltransferases: identification of amino acids determining the specificities of the aminoglycoside 6'-N-acetyltransferase Ib and IIa proteins. J Bacteriol. 1992 May;174(10):3196-203.
31	NAT1 genotypes do not predict response to mesalamine in patients with ulcerative colitis. Z Gastroenterol. 2008 Mar;46(3):259-65.
32	Xanthine oxidase inhibition by allopurinol affects the reliability of urinary caffeine metabolic ratios as markers for N-acetyltransferase 2 and CYP1A2 activities. Eur J Clin Pharmacol. 1999 Jan;54(11):869-76.
33	Aminoglycoside resistance resulting from tight drug binding to an altered aminoglycoside acetyltransferase. Antimicrob Agents Chemother. 2003 May;47(5):1577-83.
34	Effect of common NAT2 variant alleles in the acetylation of the major clonazepam metabolite, 7-aminoclonazepam. Drug Metab Lett. 2007 Jan;1(1):3-5.
35	In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions. Basic Clin Pharmacol Toxicol. 2008 Aug;103(2):157-65.
36	Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo. J Asian Nat Prod Res. 2012;14(4):382-95.
37	Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36.
38	Stiripentol. Expert Opin Investig Drugs. 2005 Jul;14(7):905-11.
39	Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52.
40	Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. Drug Metab Dispos. 2003 Nov;31(11):1352-60.
41	Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem. 2005 Jun 2;48(11):3808-15.
42	Effects of histamine H2-receptor blockade on the cardiovascular reflex response to lower-body negative pressure in man. Acta Physiol Scand. 1990 May;139(1):161-72. doi: 10.1111/j.1748-1716.1990.tb08909.x.
43	Addition of acebutolol to diuretics in hypertension. Clin Pharmacol Ther. 1981 Dec;30(6):739-44. doi: 10.1038/clpt.1981.232.
44	Relative potency of a beta-blocking and a calcium entry blocking agent as antihypertensive drugs in black patients. Eur J Clin Pharmacol. 1986;29(5):523-7. doi: 10.1007/BF00635887.
45	Influences of norepinephrine transporter function on the distribution of sympathetic activity in humans. Hypertension. 2006 Jul;48(1):120-6. doi: 10.1161/01.HYP.0000225424.13138.5d. Epub 2006 May 22.
46	Effects of sulindac and naproxen on prostaglandin excretion in patients with impaired renal function and rheumatoid arthritis. Am J Med. 1990 Sep;89(3):313-21. doi: 10.1016/0002-9343(90)90344-d.
47	Effects of an angiotensin converting enzyme inhibitor, ramipril, on intracranial circulation in healthy volunteers. off. Br J Clin Pharmacol. 1992 Sep;34(3):224-30. doi: 10.1111/j.1365-2125.1992.tb04128.x.
48	Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites. Am J Physiol Renal Physiol. 2005 May;288(5):F1044-52. doi: 10.1152/ajprenal.00142.2004. Epub 2004 Dec 21.
49	beta-Endorphin and essential hypertension: importance of the clonidine-naloxone interaction. Acta Physiol Hung. 1985;65(2):217-26.
50	Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med. 1983 Dec 8;309(23):1414-9. doi: 10.1056/NEJM198312083092303.
51	Detection of low-renin hypertension; evaluation of out-patient renin-stimulating methods. Clin Sci Mol Med. 1975 Feb;48(2):91-6. doi: 10.1042/cs0480091.