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

General Information of Drug (ID: DMQ314B)

• Drug Name: Hexobarbital Drug Info
• Synonyms: Barbidorm; Citodon; Citopan; Cyclonal; Cyclopan; Dorico; Enhexymal; Enhexymalum; Esobarbitale; Evipal; Evipan; Hexabarbital;Hexobarbitalum; Hexobarbitone; Hexobarbitonum; Methexenyl; Methylhexabarbital; Methylhexabital; Narcosan; Noctivane; Sombucaps; Sombulex; Somnalert; Esobarbitale [DCIT]; Esobarbitale [Italian]; Hexanastab oral; Sodium hexobarbital; Citopan (TN); Evipan (TN); Hexenal (barbiturate); Hexobarbital (VAN); Hexobarbital [INN:JAN]; Hexobarbitalum [INN-Latin]; Hexobarbital (JAN/INN); N-Methyl-5-cyclohexenyl-5-methylbarbituric acid; (+-)-Hexobarbital; 1,5-Dimethyl-5-(1-cyclohexenyl)barbituric acid; 2,4,6(1H,3H,5H)-Pyrimidinetrione, 5-(1-cyclohexen-1-yl)-1,5-dimethyl; 5-(1-CYCLOHEXEN-1-YL)-1,5-DIMETHYLBARBITURIC ACID; 5-(1-Cyclohexen-1-yl)-1,5-dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrione; 5-(1-Cyclohexenyl)-1,5-dimethylbarbituric acid; 5-(1-Cyclohexenyl-1)-1-methyl-5-methylbarbituric acid; 5-(cyclohex-1-en-1-yl)-1,5-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione; 5-(cyclohexen-1-yl)-1,5-dimethyl-1,3-diazinane-2,4,6-trione; 5-(delta-1,2-Cyclohexenyl)-5-methyl-N-methyl-barbitursaeure [German]; 5-(delta-1,2-cyclohexenyl)-5-methyl-N-methyl-barbitursaeure; 5-(delta.-1,2-cyclohexenyl)-5-methyl-N-methyl-barbitursaeure; 5-cyclohex-1-en-1-yl-1,5-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione; 5-cyclohex-1-en-1-yl-2-hydroxy-1,5-dimethylpyrimidine-4,6(1H,5H)-dione

Indication

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[1]

• Therapeutic Class: Hypnotics and Sedatives
• Cross-matching ID:
  PubChem CID: 3608
  ChEBI ID: CHEBI:5706
  CAS Number: CAS 56-29-1
  TTD Drug ID: DMQ314B
  INTEDE Drug ID: DR0809

Molecule-Related Drug Atlas

Drug(s) Targeting GABA(A) receptor alpha-1 (GABRA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[2]
Zolpidem	DMWOSKJ	Insomnia	7A00-7A0Z	Approved	[7]
Methoxyflurane	DML0RAE	Anaesthesia	9A78.6	Approved	[2]
Nitrazepam	DMEGIQ6	Epilepsy	8A60-8A68	Approved	[2]
Allopregnanolone	DMNLHAC	Depression	6A70-6A7Z	approved	[8]
Clobazam - Lundbeck	DMW1OQ0	Anxiety disorder	6B00-6B0Z	Approved	[2]
THIOCOLCHICOSIDE	DMEPWYA	Muscle spasm	MB47.3	Approved	[9]
Meprobamate	DMHM93Y	Anxiety		Approved	[2]
Zaleplon	DMGFWSM	Insomnia	7A00-7A0Z	Approved	[10]
Ethchlorvynol	DM53IP1	Insomnia	7A00-7A0Z	Approved	[2]

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	[11]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[12]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[17]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[18]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[12]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[6]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[19]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[20]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[21]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[22]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[23]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[17]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[25]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[26]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[27]

Drug(s) Metabolized By Cytochrome P450 2C9 (CYP2C9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[28]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[29]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[30]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[4]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[31]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[4]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[32]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[33]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[34]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[35]

Drug(s) Metabolized By Mephenytoin 4-hydroxylase (CYP2C19)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[36]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[28]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[37]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[38]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[4]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[39]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[40]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[35]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[41]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[42]

Drug(s) Metabolized By Prostaglandin G/H synthase 1 (COX-1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[6]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[43]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[6]
Diazepam	DM08E9O	Alcohol withdrawal		Approved	[6]
Dapsone	DM4LT8A	Acne vulgaris	ED80	Approved	[6]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[6]
Nateglinide	DMLK2QH	Diabetic complication	5A2Y	Approved	[6]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[6]
Ketobemidone	DMM3L6Z	Pain	MG30-MG3Z	Approved	[6]
Irbesartan	DMTP1DC	Diabetic kidney disease	GB61.Z	Approved	[6]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
GABA(A) receptor alpha-1 (GABRA1)	TT1MPAY	GBRA1_HUMAN	Antagonist	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[4]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[5]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[3]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Substrate	[6]

References

• [1] Drug information of Hexobarbital, 2008. eduDrugs.
• [2] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [3] Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. The role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase. Drug Metab Dispos. 1994 Nov-Dec;22(6):909-15.
• [4] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [5] Stereoselective hexobarbital 3'-hydroxylation by CYP2C19 expressed in yeast cells and the roles of amino acid residues at positions 300 and 476. Chirality. 2007 Jul;19(7):550-8.
• [6] 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.
• [7] Zolpidem, a selective GABA(A) receptor alpha1 subunit agonist, induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat.Brain Res Bull.2006 Dec 11;71(1-3):200-7.
• [8] Neurosteroid analogues. 10. The effect of methyl group substitution at the C-6 and C-7 positions on the GABA modulatory and anesthetic actions of (... J Med Chem. 2005 Apr 21;48(8):3051-9.
• [9] 3-demethoxy-3-glycosylaminothiocolchicines: Synthesis of a new class of putative muscle relaxant compounds. J Med Chem. 2006 Sep 7;49(18):5571-7.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [11] 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.
• [12] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [13] 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.
• [14] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [15] 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.
• [16] 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.
• [17] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [22] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [23] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [24] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [25] 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.
• [26] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [27] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
• [28] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [29] Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
• [30] Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
• [31] Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
• [32] Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
• [33] New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
• [34] A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
• [35] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [36] High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
• [37] Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
• [38] CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
• [39] Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
• [40] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [41] Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
• [42] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [43] Peroxidative free radical formation and O-demethylation of etoposide(VP-16) and teniposide(VM-26). Biochem Biophys Res Commun. 1986 Feb 26;135(1):215-20.