DrugBank: Methsuximide (DB05246)

targets (1) enzymes (1)

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

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 [inn-spanish]
Mesuximide
Mesuximidum [inn-latin]
Methsuximid
Metosuccimmide [DCIT]
Metsuccimide
N-methyl-alpha-methyl-alpha-phenylsuccinimide
N,2-Dimethyl-2-phenylsuccinimide

Brand names

Celontin
Petinutin

Brand name mixtures

Not Available

Categories

Anticonvulsants
Succinimides

CAS number

77-41-8

Weight

Average: 203.2371
Monoisotopic: 203.094628665

Chemical Formula

C₁₂H₁₃NO₂

InChI Key

InChIKey=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

Plain Text

IUPAC Name

1,3-dimethyl-3-phenylpyrrolidine-2,5-dione

SMILES

CN1C(=O)CC(C)(C1=O)C1=CC=CC=C1

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Phenethylamines
Phenylpropylamines
Gamma Lactams

Substructures

Carbonyl Compounds
Amino Ketones
Pyrrolidines
Benzene and Derivatives
Phenethylamines
Heterocyclic compounds
Aromatic compounds
Carboxamides and Derivatives
Phenylpropylamines
Carboxylic Acids and Derivatives
Gamma Lactams

Pharmacology

Indication

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

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.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

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

Pharmacoeconomics

Manufacturers

Parke davis div warner lambert co

Packagers

Farmea
Kaiser Foundation Hospital
Pfizer Inc.

Dosage forms

Form	Route	Strength
Capsule	Oral

Prices

Unit description	Cost	Unit
Celontin 300 mg kapseal	1.53 USD	each
Celontin 300 mg Capsule	1.1 USD	capsule

Patents

Not Available

Properties

State

solid

Melting point

52.5 oC

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
water solubility	2.13e+00 g/l	ALOGPS
logP	1.46	ALOGPS
logP	1.46	ChemAxon Molconvert
logS	-1.98	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	2	ChemAxon Molconvert
hydrogen donor count	0	ChemAxon Molconvert
polar surface area	37.38	ChemAxon Molconvert
rotatable bond count	1	ChemAxon Molconvert
refractivity	56.35	ChemAxon Molconvert
polarizability	21.40	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Hurst DL: Methsuximide therapy of juvenile myoclonic epilepsy. Seizure. 1996 Mar;5(1):47-50. Pubmed
Besag FM, Berry DJ, Pool F: Methsuximide lowers lamotrigine blood levels: A pharmacokinetic antiepileptic drug interaction. Epilepsia. 2000 May;41(5):624-7. Pubmed

External Links

Resource	Link
PubChem Compound	6476
PubChem Substance	46505339
ChemSpider	6231
Therapeutic Targets Database	DAP001253
PharmGKB	PA450438
Drug Product Database	22802
RxList	http://www.rxlist.com/cgi/generic/methsuximide.htm
Drugs.com	http://www.drugs.com/cdi/methsuximide.html
Wikipedia	http://en.wikipedia.org/wiki/Methsuximide

ATC Codes

N03AD03

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Avoid alcohol
Take with food

Targets
1. Voltage-dependent T-type calcium channel subunit alpha-1G Pharmacological action: yes Actions: inhibitor 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 Organism class: human UniProt ID: O43497 Gene: CACNA1G Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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. Pubmed 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

Targets

1. Voltage-dependent T-type calcium channel subunit alpha-1G

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: O43497 Link_out

Gene: CACNA1G Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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. Pubmed
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

Enzymes
1. Cytochrome P450 2C19 Actions: substrate, inhibitor 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 UniProt ID: P33261 Gene: CYP2C19 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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. Epub 2009 Nov 24. Pubmed

Enzymes

1. Cytochrome P450 2C19

Actions: substrate, inhibitor

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

UniProt ID: P33261 Link_out

Gene: CYP2C19 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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. Epub 2009 Nov 24. Pubmed

Comments

Drug created on October 30, 2007 19:03 / Updated on January 02, 2011 09:38

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.