General Information of Drug (ID: DMR5ZUP)

Drug Name
Paramethadione
Synonyms
Isoethadione; Paradione; Parametadiona; Parametadione; Paramethadionum; Parametadione [DCIT]; A 348; Paradione (TN); Parametadiona [INN-Spanish]; Paramethadione (INN); Paramethadione [BAN:INN]; Paramethadione [INN:BAN]; Paramethadionum [INN-Latin]; 3,5-Dimethyl-5-ethyloxazolidine-2,4-dione; 5-Ethyl-3,5-dimethyl-1,3-oxazolidine-2,4-dione; 5-Ethyl-3,5-dimethyl-2,4-oxazolidinedione
Indication
Disease Entry ICD 11 Status REF
Fetal trimethadione syndrome LD2F.0Y Approved [1], [2], [3]
Seizure disorder 8A6Z Approved [1], [2], [3]
Therapeutic Class
Anticonvulsants
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 157.17
Topological Polar Surface Area (xlogp) 0.8
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Absorption
The drug is rapidly absorbed via the digestive tract [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 12 - 24 hours [5]
Metabolism
The drug is metabolized via the hepatic [4]
Chemical Identifiers
Formula
C7H11NO3
IUPAC Name
5-ethyl-3,5-dimethyl-1,3-oxazolidine-2,4-dione
Canonical SMILES
CCC1(C(=O)N(C(=O)O1)C)C
InChI
InChI=1S/C7H11NO3/c1-4-7(2)5(9)8(3)6(10)11-7/h4H2,1-3H3
InChIKey
VQASKUSHBVDKGU-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
8280
ChEBI ID
CHEBI:7921
CAS Number
115-67-3
DrugBank ID
DB00617
TTD ID
D09JBP
INTEDE ID
DR1239

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Voltage-gated calcium channel alpha Cav3.1 (CACNA1G) TT729IR CAC1G_HUMAN Blocker [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Substrate [8]
Cytochrome P450 2C9 (CYP2C9)
Main DME
DE5IED8 CP2C9_HUMAN Substrate [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Paramethadione (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Levomilnacipran DMV26S8 Moderate Antagonize the effect of Paramethadione when combined with Levomilnacipran. Chronic pain [MG30] [44]
Olopatadine DMKMWQG Moderate Additive CNS depression effects by the combination of Paramethadione and Olopatadine. Conjunctiva disorder [9A60] [45]
Ethanol DMDRQZU Moderate Additive CNS depression effects by the combination of Paramethadione and Ethanol. Cystitis [GC00] [45]
Sertraline DM0FB1J Moderate Antagonize the effect of Paramethadione when combined with Sertraline. Depression [6A70-6A7Z] [44]
Vilazodone DM4LECQ Moderate Antagonize the effect of Paramethadione when combined with Vilazodone. Depression [6A70-6A7Z] [44]
Paroxetine DM5PVQE Moderate Antagonize the effect of Paramethadione when combined with Paroxetine. Depression [6A70-6A7Z] [44]
Vortioxetine DM6F1PU Moderate Antagonize the effect of Paramethadione when combined with Vortioxetine. Depression [6A70-6A7Z] [44]
Milnacipran DMBFE74 Moderate Antagonize the effect of Paramethadione when combined with Milnacipran. Depression [6A70-6A7Z] [44]
Escitalopram DMFK9HG Moderate Antagonize the effect of Paramethadione when combined with Escitalopram. Depression [6A70-6A7Z] [44]
Desvenlafaxine DMHD4PE Moderate Antagonize the effect of Paramethadione when combined with Desvenlafaxine. Depression [6A70-6A7Z] [44]
Esketamine DMVU687 Moderate Additive CNS depression effects by the combination of Paramethadione and Esketamine. Depression [6A70-6A7Z] [46]
Hydroxychloroquine DMSIVND Moderate Antagonize the effect of Paramethadione when combined with Hydroxychloroquine. Malaria [1F40-1F45] [46]
Allopregnanolone DMNLHAC Moderate Additive CNS depression effects by the combination of Paramethadione and Allopregnanolone. Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z] [47]
Lasmiditan DMXLVDT Moderate Additive CNS depression effects by the combination of Paramethadione and Lasmiditan. Migraine [8A80] [48]
Flibanserin DM70DTN Moderate Additive CNS depression effects by the combination of Paramethadione and Flibanserin. Mood disorder [6A60-6E23] [49]
Thalidomide DM70BU5 Moderate Additive CNS depression effects by the combination of Paramethadione and Thalidomide. Multiple myeloma [2A83] [45]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Paramethadione and Ocrelizumab. Multiple sclerosis [8A40] [50]
Omacetaxine mepesuccinate DMPU2WX Moderate Additive immunosuppressive effects by the combination of Paramethadione and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [51]
Apraclonidine DMO4PVE Moderate Additive CNS depression effects by the combination of Paramethadione and Apraclonidine. Optic nerve disorder [9C40] [52]
Dextropropoxyphene DM23HCX Major Additive CNS depression effects by the combination of Paramethadione and Dextropropoxyphene. Pain [MG30-MG3Z] [53]
Buprenorphine DMPRI8G Major Additive CNS depression effects by the combination of Paramethadione and Buprenorphine. Pain [MG30-MG3Z] [54]
Tizanidine DMR2IQ4 Moderate Additive CNS depression effects by the combination of Paramethadione and Tizanidine. Tonus and reflex abnormality [MB47] [55]
Ganciclovir DM1MBYQ Moderate Additive myelosuppressive effects by the combination of Paramethadione and Ganciclovir. Virus infection [1A24-1D9Z] [46]
Valganciclovir DMS2IUH Moderate Additive myelosuppressive effects by the combination of Paramethadione and Valganciclovir. Virus infection [1A24-1D9Z] [46]
⏷ Show the Full List of 24 DDI Information of This Drug

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: 7261).
2 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 006800.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss. Hear Res. 2007 Apr;226(1-2):52-60.
7 Involvement of cytochrome P450 2C9, 2E1 and 3A4 in trimethadione N-demethylation in human microsomes. J Clin Pharm Ther. 2003 Dec;28(6):493-6.
8 Cytochrome P450 2E1: its clinical and toxicological role. J Clin Pharm Ther. 2000 Jun;25(3):165-75.
9 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.
10 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
11 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.
12 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
13 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.
14 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.
15 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
16 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.
17 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.
18 Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol. 2005 Jul;289(1):G54-63.
19 Cytochrome P450 2E1 null mice provide novel protection against cisplatin-induced nephrotoxicity and apoptosis. Kidney Int. 2003 May;63(5):1687-96.
20 Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
21 Acetaminophen induced acute liver failure via oxidative stress and JNK activation: protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res. 2010 Mar;44(3):340-55.
22 A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther. 1998 Sep;286(3):1294-300.
23 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.
24 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
25 Novel metabolic pathway of estrone and 17beta-estradiol catalyzed by cytochrome P-450. Drug Metab Dispos. 2000 Feb;28(2):110-2.
26 Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes. Biochem Pharmacol. 2002 Oct 1;64(7):1151-6.
27 CYP2E1 and clinical features in alcoholics. Neuropsychobiology. 2003;47(2):86-9.
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 Mechanism of tissue-selective drug action in the cardiovascular system. Mol Interv. 2005 Apr;5(2):84-93.
37 Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions. J Neurosci. 2008 Nov 12;28(46):11959-69.
38 Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol Pharmacol. 2001 Nov;60(5):1121-32.
39 Differential inhibition of T-type calcium channels by neuroleptics. J Neurosci. 2002 Jan 15;22(2):396-403.
40 Pfizer. Product Development Pipeline. March 31 2009.
41 The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Dec 21;2(12):730-742.
42 Discovery of potent T-type calcium channel blocker. Bioorg Med Chem Lett. 2007 Nov 1;17(21):5740-3.
43 Synthesis and biological evaluation of novel T-type calcium channel blockers. Bioorg Med Chem Lett. 2007 Jan 15;17(2):471-5.
44 Belcastro V, Costa C, Striano P "Levetiracetam-associated hyponatremia." Seizure 17 (2008): 389-90. [PMID: 18584781]
45 Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]
46 Cerner Multum, Inc. "Australian Product Information.".
47 Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
48 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
49 Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
50 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
51 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
52 Product Information. Alphagan (brimonidine ophthalmic). Allergan Inc, Irvine, CA.
53 Hansen BS, Dam M, Brandt J, et al "Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man." Acta Neurol Scand 61 (1980): 357-67. [PMID: 6998251]
54 Sekar M, Mimpriss TJ "Buprenorphine, benzodiazepines and prolonged respiratory depression." Anaesthesia 42 (1987): 567-8. [PMID: 3592200]
55 Product Information. Zanaflex (tizanidine). Acorda Therapeutics, Hawthorne, NY.