Identification

Name
Methsuximide
Accession Number
DB05246
Type
Small Molecule
Groups
Approved
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
  • Mesuximida
  • Mesuximide
  • Mesuximidum
  • Methsuximid
  • Metosuccimmide
  • Metsuccimide
  • N-methyl-alpha-methyl-alpha-phenylsuccinimide
  • N,2-Dimethyl-2-phenylsuccinimide
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CelontinCapsule150 mg/1OralPARKE-DAVIS2006-11-032006-11-03Us
CelontinCapsule300 mg/1OralParke Davis Div Of Pfizer Inc1957-02-08Not applicableUs
Celontin Cap 300mgCapsule300 mgOralErfa Canada 2012 Inc1957-12-312015-06-05Canada
International/Other Brands
Celontin / Petinutin
Categories
UNII
0G76K8X6C0
CAS number
77-41-8
Weight
Average: 203.2371
Monoisotopic: 203.094628665
Chemical Formula
C12H13NO2
InChI Key
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

Pharmacology

Indication

For the control of absence (petit mal) seizures that are refractory to other drugs.

Associated Conditions
Pharmacodynamics

Used 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 action

Binds 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.

TargetActionsOrganism
AVoltage-dependent T-type calcium channel subunit alpha-1G
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

1.4-2.6 hours for mesuximide and 28-38 hours for the active metabolite.

Clearance
Not Available
Toxicity

Acute 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Methsuximide is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineMethsuximide may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Methsuximide is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Methsuximide is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Methsuximide is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Methsuximide is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineMethsuximide may increase the excretion rate of 6-O-benzylguanine which could result in a lower serum level and potentially a reduction in efficacy.
7-DeazaguanineMethsuximide may increase the excretion rate of 7-Deazaguanine which could result in a lower serum level and potentially a reduction in efficacy.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Methsuximide is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Methsuximide is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
Food Interactions
  • Avoid alcohol
  • Take with food

References

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]
  3. Wright JD, Helsby NA, Ward SA: The role of S-mephenytoin hydroxylase (CYP2C19) in the metabolism of the antimalarial biguanides. Br J Clin Pharmacol. 1995 Apr;39(4):441-4. [PubMed:7640152]
External Links
Human Metabolome Database
HMDB0015611
PubChem Compound
6476
PubChem Substance
46505339
ChemSpider
6231
ChEBI
6846
ChEMBL
CHEMBL697
Therapeutic Targets Database
DAP001253
PharmGKB
PA164743145
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Methsuximide
ATC Codes
N03AD03 — Mesuximide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Farmea
  • Kaiser Foundation Hospital
  • Pfizer Inc.
Dosage forms
FormRouteStrength
CapsuleOral150 mg/1
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)52.5 °CPhysProp
boiling point (°C)121.5 °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 RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-014i-3910000000-9cae394b5b94a483c401
GC-MS Spectrum - CI-BGC-MSsplash10-0udi-0090000000-31b6e0b0429306f0d6da
GC-MS Spectrum - CI-BGC-MSsplash10-0udi-0490000000-37eb2b7cfbb3d8b42e97
Mass Spectrum (Electron Ionization)MSsplash10-014i-4910000000-aa3742fc04cdbcda351f
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0390000000-00d729cf9e85b7d75068
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-1690000000-0a263ad37a0831b81fb3
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-4910000000-eb0a383017c0566e6a11
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014l-9800000000-5df2aae06682d9488eef
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05mo-9400000000-6de622fc3efce00a0b34
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-052f-9300000000-1e2faae8b516a3fc7ad5

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyrrolidines
Sub Class
Phenylpyrrolidines
Direct Parent
Phenylpyrrolidines
Alternative Parents
Pyrrolidine-2-ones / N-substituted carboxylic acid imides / N-alkylpyrrolidines / Benzene and substituted derivatives / Pyrroles / Dicarboximides / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds
show 3 more
Substituents
3-phenylpyrrolidine / Monocyclic benzene moiety / Carboxylic acid imide, n-substituted / Pyrrolidone / 2-pyrrolidone / N-alkylpyrrolidine / Benzenoid / Carboxylic acid imide / Dicarboximide / Pyrrole
show 12 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

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, hor...
Gene Name
CACNA1G
Uniprot ID
O43497
Uniprot Name
Voltage-dependent T-type calcium channel subunit alpha-1G
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
Substrate
Inhibitor
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
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]
  2. Wright JD, Helsby NA, Ward SA: The role of S-mephenytoin hydroxylase (CYP2C19) in the metabolism of the antimalarial biguanides. Br J Clin Pharmacol. 1995 Apr;39(4):441-4. [PubMed:7640152]

Drug created on October 30, 2007 19:03 / Updated on October 01, 2018 14:00