Identification
- Generic Name
- Paramethadione
- DrugBank Accession Number
- DB00617
- Background
Paramethadione is an anticonvulsant in the oxazolidinedione class. It is associated with fetal trimethadione syndrome, which is also known as paramethadione syndrome.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Paramethadione (DB00617)
- Weight
- Average: 157.1671
Monoisotopic: 157.073893223 - Chemical Formula
- C7H11NO3
- Synonyms
- Parametadiona
- Parametadione
- Paramethadione
- Paramethadionum
Pharmacology
- Indication
Used for the control of absence (petit mal) seizures that are refractory to treatment with other medications.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Paramethadione is an oxazolidinedione anticonvulsant similar to trimethadione that acts on the central nervous system (CNS) to reduce the number of absence seizures (often seen in epileptics). Absence seizures involve an interruption to consciousness where the person experiencing the seizure seems to become vacant and unresponsive for a short period of time (usually up to 30 seconds). Paramethadione acts on thalamic neurons in the thalamic reticular nucleus (which studies have shown to be associated with absence seizures, von Krosigk et al., 1993).
- Mechanism of action
Dione anticonvulsants such as paramethadione reduce T-type calcium currents in thalamic neurons (including thalamic relay neurons). This inhibits corticothalamic transmission and raises the threshold for repetitive activity in the thalamus. This results in a dampening of the abnormal thalamocortical rhythmicity proposed to underlie the 3-Hz spike-and-wave discharge seen on electroencephalogram (EEG) during absence seizures.
Target Actions Organism AVoltage-dependent T-type calcium channel subunit alpha-1I inhibitorHumans - Absorption
Rapid via the digestive tract.
- Volume of distribution
Not Available
- Protein binding
Not significant
- Metabolism
Primarily hepatic (mainly via cytochrome P450 isozyme 2C9), paramethadione is completely demethylated to 5-ethyl-5-methyl-2,4-oxazolidinedione, the active metabolite.
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- Route of elimination
Not Available
- Half-life
12 to 24 hours (however the half-life for the active metabolite is not known)
- Clearance
Not Available
- Adverse Effects
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Symptoms of overdose include clumsiness or unsteadiness, coma, severe dizziness, severe drowsiness, severe nausea, and problems with vision.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Paramethadione is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Paramethadione can be increased when it is combined with Abametapir. Abatacept The metabolism of Paramethadione can be increased when combined with Abatacept. Abiraterone The metabolism of Paramethadione can be decreased when combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Paramethadione. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Paradione
Categories
- ATC Codes
- N03AC01 — Paramethadione
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as oxazolidinediones. These are compounds containing an oxazolidine ring which bears two ketones.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azolidines
- Sub Class
- Oxazolidines
- Direct Parent
- Oxazolidinediones
- Alternative Parents
- Dicarboximides / Carbamate esters / Organic carbonic acids and derivatives / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Aliphatic heteromonocyclic compound / Azacycle / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Carboxylic acid derivative / Dicarboximide / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- oxazolidinone (CHEBI:7921)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Z615FRW64N
- CAS number
- 115-67-3
- InChI Key
- VQASKUSHBVDKGU-UHFFFAOYSA-N
- InChI
- InChI=1S/C7H11NO3/c1-4-7(2)5(9)8(3)6(10)11-7/h4H2,1-3H3
- IUPAC Name
- 5-ethyl-3,5-dimethyl-1,3-oxazolidine-2,4-dione
- SMILES
- CCC1(C)OC(=O)N(C)C1=O
References
- General References
- Hoffman DJ, Chun AH: Paramethadione and metabolite serum levels in humans after a single oral paramethadione dose. J Pharm Sci. 1975 Oct;64(10):1702-3. [Article]
- Feldman GL, Weaver DD, Lovrien EW: The fetal trimethadione syndrome: report of an additional family and further delineation of this syndrome. Am J Dis Child. 1977 Dec;131(12):1389-92. [Article]
- External Links
- Human Metabolome Database
- HMDB0014755
- KEGG Drug
- D00495
- KEGG Compound
- C07411
- PubChem Compound
- 8280
- PubChem Substance
- 46509173
- ChemSpider
- 7979
- 32894
- ChEBI
- 7921
- ChEMBL
- CHEMBL1100
- Therapeutic Targets Database
- DAP001266
- PharmGKB
- PA164748880
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Paramethadione
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Abbott laboratories pharmaceutical products div
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source boiling point (°C) 101.5 °C Not Available water solubility 8.4 mg/mL Not Available logP 0.3 Not Available - Predicted Properties
Property Value Source Water Solubility 135.0 mg/mL ALOGPS logP 0.9 ALOGPS logP 1.03 Chemaxon logS -0.07 ALOGPS Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 46.61 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 37.72 m3·mol-1 Chemaxon Polarizability 15.39 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9955 Blood Brain Barrier + 0.9804 Caco-2 permeable + 0.5334 P-glycoprotein substrate Non-substrate 0.8117 P-glycoprotein inhibitor I Non-inhibitor 0.5232 P-glycoprotein inhibitor II Non-inhibitor 0.5937 Renal organic cation transporter Non-inhibitor 0.9572 CYP450 2C9 substrate Non-substrate 0.8651 CYP450 2D6 substrate Non-substrate 0.8869 CYP450 3A4 substrate Substrate 0.5517 CYP450 1A2 substrate Non-inhibitor 0.8174 CYP450 2C9 inhibitor Non-inhibitor 0.812 CYP450 2D6 inhibitor Non-inhibitor 0.914 CYP450 2C19 inhibitor Non-inhibitor 0.7845 CYP450 3A4 inhibitor Non-inhibitor 0.8711 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8976 Ames test Non AMES toxic 0.7081 Carcinogenicity Non-carcinogens 0.8298 Biodegradation Not ready biodegradable 0.8515 Rat acute toxicity 2.2682 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9921 hERG inhibition (predictor II) Non-inhibitor 0.9752
Spectra
- Mass Spec (NIST)
- Download (7.42 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 133.6933912 predictedDarkChem Lite v0.1.0 [M-H]- 132.64555 predictedDeepCCS 1.0 (2019) [M+H]+ 134.3090912 predictedDarkChem Lite v0.1.0 [M+H]+ 136.47289 predictedDeepCCS 1.0 (2019) [M+Na]+ 134.0983912 predictedDarkChem Lite v0.1.0 [M+Na]+ 145.44188 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
- Gene Name
- CACNA1I
- Uniprot ID
- Q9P0X4
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1I
- Molecular Weight
- 245100.8 Da
References
- Gaspar HA, Breen G: Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach. Sci Rep. 2017 Sep 29;7(1):12460. doi: 10.1038/s41598-017-12325-3. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Kurata N, Nishimura Y, Iwase M, Fischer NE, Tang BK, Inaba T, Yasuhara H: Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica. 1998 Nov;28(11):1041-7. [Article]
- Tanaka E, Terada M, Misawa S: Cytochrome P450 2E1: its clinical and toxicological role. J Clin Pharm Ther. 2000 Jun;25(3):165-75. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Tanaka E, Kurata N, Yasuhara H: 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. [Article]
- Kurata N, Nishimura Y, Iwase M, Fischer NE, Tang BK, Inaba T, Yasuhara H: Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica. 1998 Nov;28(11):1041-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- This enzyme effect is supported only by 1 in vitro study.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Tanaka E, Kurata N, Yasuhara H: 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Kurata N, Nishimura Y, Iwase M, Fischer NE, Tang BK, Inaba T, Yasuhara H: Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1. Xenobiotica. 1998 Nov;28(11):1041-7. [Article]
Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 06:53