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Identification
NameMethsuximide
Accession NumberDB05246
TypeSmall Molecule
GroupsApproved
Description

Mesuximide (or methsuximide) is an anticonvulsant medication. It is sold by Pfizer under the name Petinutin. [Wikipedia]

Structure
Thumb
Synonyms
(RS)-1,3-Dimethyl-3-phenyl-2,5-pyrrolidindion
1,3-Dimethyl-3-phenyl-2,5-dioxopyrrolidine
1,3-Dimethyl-3-phenyl-2,5-pyrrolidinedione
1,3-Dimethyl-3-phenyl-pyrrolidin-2,5-dione
1,3-Dimethyl-3-phenylsuccinimide
Alpha-methyl-alpha-phenyl n-methyl succinimide
Alpha-methylphensuximide
Celontin
Mesuximida
Mesuximide
Mesuximidum
Methsuximid
Metosuccimmide
Metsuccimide
N-methyl-alpha-methyl-alpha-phenylsuccinimide
N,2-Dimethyl-2-phenylsuccinimide
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Celontincapsule300 mg/1oralParke Davis Div Of Pfizer Inc1957-02-08Not applicableUs
Celontin Cap 300mgcapsule300 mgoralErfa Canada 2012 Inc1957-12-312015-06-05Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
PetinutinNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII0G76K8X6C0
CAS number77-41-8
WeightAverage: 203.2371
Monoisotopic: 203.094628665
Chemical FormulaC12H13NO2
InChI KeyInChIKey=AJXPJJZHWIXJCJ-UHFFFAOYSA-N
InChI
InChI=1S/C12H13NO2/c1-12(9-6-4-3-5-7-9)8-10(14)13(2)11(12)15/h3-7H,8H2,1-2H3
IUPAC Name
1,3-dimethyl-3-phenylpyrrolidine-2,5-dione
SMILES
CN1C(=O)CC(C)(C1=O)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpyrrolidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrrolidine ring through a CC or CN bond. Pyrrolidine is a five-membered saturated aliphatic heterocycle with one nitrogen atom and four carbon atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyrrolidines
Sub ClassPhenylpyrrolidines
Direct ParentPhenylpyrrolidines
Alternative Parents
Substituents
  • 3-phenylpyrrolidine
  • Dicarboximide
  • Benzenoid
  • N-alkylpyrrolidine
  • 2-pyrrolidone
  • Pyrrolidone
  • Carboxylic acid imide, n-substituted
  • Monocyclic benzene moiety
  • Pyrrole
  • Carboxylic acid imide
  • Tertiary amine
  • Lactam
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the control of absence (petit mal) seizures that are refractory to other drugs.
PharmacodynamicsUsed in the treatment of epilepsy. Methsuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli.
Mechanism of actionBinds to T-type voltage sensitive calcium channels. 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, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life1.4-2.6 hours for mesuximide and 28-38 hours for the active metabolite.
ClearanceNot Available
ToxicityAcute overdoses may produce nausea, vomiting, and CNS depression including coma with respiratory depression. Levels greater than 40 µg/mL have caused toxicity and coma has been seen at levels of 150 µg/mL.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9967
Caco-2 permeable+0.6968
P-glycoprotein substrateNon-substrate0.7118
P-glycoprotein inhibitor INon-inhibitor0.8599
P-glycoprotein inhibitor IINon-inhibitor0.9433
Renal organic cation transporterNon-inhibitor0.7784
CYP450 2C9 substrateNon-substrate0.7943
CYP450 2D6 substrateNon-substrate0.8923
CYP450 3A4 substrateSubstrate0.6004
CYP450 1A2 substrateNon-inhibitor0.888
CYP450 2C9 inhibitorNon-inhibitor0.8882
CYP450 2D6 inhibitorNon-inhibitor0.922
CYP450 2C19 inhibitorNon-inhibitor0.845
CYP450 3A4 inhibitorNon-inhibitor0.9748
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9629
Ames testNon AMES toxic0.9099
CarcinogenicityNon-carcinogens0.8355
BiodegradationNot ready biodegradable0.8265
Rat acute toxicity2.1961 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9942
hERG inhibition (predictor II)Non-inhibitor0.9625
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral300 mg/1
Capsuleoral300 mg
Prices
Unit descriptionCostUnit
Celontin 300 mg kapseal1.53USD each
Celontin 300 mg Capsule1.1USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point52.5 °CPhysProp
boiling point121.5 °C at 1.00E-01 mm HgPhysProp
Predicted Properties
PropertyValueSource
Water Solubility2.13 mg/mLALOGPS
logP1.46ALOGPS
logP1.46ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)19.03ChemAxon
pKa (Strongest Basic)-7.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area37.38 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity56.35 m3·mol-1ChemAxon
Polarizability21.4 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-014i-4910000000-aa3742fc04cdbcda351fView in MoNA
References
Synthesis ReferenceNot Available
General References
  1. Hurst DL: Methsuximide therapy of juvenile myoclonic epilepsy. Seizure. 1996 Mar;5(1):47-50. [PubMed:8777552 ]
  2. Besag FM, Berry DJ, Pool F: Methsuximide lowers lamotrigine blood levels: A pharmacokinetic antiepileptic drug interaction. Epilepsia. 2000 May;41(5):624-7. [PubMed:10802770 ]
External Links
ATC CodesN03AD03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AzelastineMethsuximide may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Methsuximide.
BortezomibThe metabolism of Methsuximide can be decreased when combined with Bortezomib.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Methsuximide.
BuprenorphineMethsuximide may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
DabrafenibThe serum concentration of Methsuximide can be decreased when it is combined with Dabrafenib.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Methsuximide.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Methsuximide.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Methsuximide.
EthanolMethsuximide may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
FluvoxamineThe metabolism of Methsuximide can be decreased when combined with Fluvoxamine.
HydrocodoneMethsuximide may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Methsuximide.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Methsuximide.
LuliconazoleThe serum concentration of Methsuximide can be increased when it is combined with Luliconazole.
LumacaftorThe serum concentration of Methsuximide can be decreased when it is combined with Lumacaftor.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Methsuximide.
MefloquineThe therapeutic efficacy of Methsuximide can be decreased when used in combination with Mefloquine.
MethotrimeprazineMethsuximide may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
MetyrosineMethsuximide may increase the sedative activities of Metyrosine.
MianserinThe therapeutic efficacy of Methsuximide can be decreased when used in combination with Mianserin.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Methsuximide.
MirtazapineMethsuximide may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Methsuximide.
OrlistatThe serum concentration of Methsuximide can be decreased when it is combined with Orlistat.
OrphenadrineMethsuximide may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
ParaldehydeMethsuximide may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineThe risk or severity of adverse effects can be increased when Methsuximide is combined with Paroxetine.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Methsuximide.
PhenytoinThe metabolism of Methsuximide can be increased when combined with Phenytoin.
PramipexoleMethsuximide may increase the sedative activities of Pramipexole.
RopiniroleMethsuximide may increase the sedative activities of Ropinirole.
RotigotineMethsuximide may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Methsuximide.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Methsuximide.
SuvorexantMethsuximide may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Methsuximide.
ThalidomideMethsuximide may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
ZolpidemMethsuximide may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food Interactions
  • Avoid alcohol
  • Take with food

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Scaffold protein binding
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, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-v...
Gene Name:
CACNA1G
Uniprot ID:
O43497
Molecular Weight:
262468.62 Da
References
  1. Gomora JC, Daud AN, Weiergraber M, Perez-Reyes E: Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol Pharmacol. 2001 Nov;60(5):1121-32. [PubMed:11641441 ]
  2. Coulter DA, Huguenard JR, Prince DA: Characterization of ethosuximide reduction of low-threshold calcium current in thalamic neurons. Ann Neurol. 1989 Jun;25(6):582-93. [PubMed:2545161 ]
  3. Wang G, Thompson SM: 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. doi: 10.1523/JNEUROSCI.3296-08.2008. [PubMed:19005061 ]
  4. Matthews EA, Dickenson AH: Effects of ethosuximide, a T-type Ca(2+) channel blocker, on dorsal horn neuronal responses in rats. Eur J Pharmacol. 2001 Mar;415(2-3):141-9. [PubMed:11274992 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on October 30, 2007 19:03 / Updated on August 17, 2016 12:24