Identification

Name
Phensuximide
Accession Number
DB00832  (APRD00496)
Type
Small Molecule
Groups
Approved
Description

Phensuximide is an anticonvulsant in the succinimide class. It suppresses the paroxysmal three cycle per second spike and wave EEG pattern associated with lapses of consciousness in petit mal seizures. The frequency of attacks is reduced by depression of nerve transmission in the motor cortex.

Structure
Thumb
Synonyms
  • Fensuccimide
  • Fensuximida
  • Phensuximide
  • Phensuximidum
External IDs
P-D 393
International/Other Brands
Lifene (Debat) / Milontin (Parke-Davis) / Milonton (BCM Corporation) / Succitimal (Katwijk )
Categories
UNII
6WVL9C355G
CAS number
86-34-0
Weight
Average: 189.2105
Monoisotopic: 189.078978601
Chemical Formula
C11H11NO2
InChI Key
WLWFNJKHKGIJNW-UHFFFAOYSA-N
InChI
InChI=1S/C11H11NO2/c1-12-10(13)7-9(11(12)14)8-5-3-2-4-6-8/h2-6,9H,7H2,1H3
IUPAC Name
1-methyl-3-phenylpyrrolidine-2,5-dione
SMILES
CN1C(=O)CC(C1=O)C1=CC=CC=C1

Pharmacology

Indication

For the treatment of epilepsy.

Structured Indications
Not Available
Pharmacodynamics

Phensuximide suppresses the paroxysmal three cycle per second spike and wave EEG pattern associated with lapses of consciousness in absence (petit mal) seizures. The frequency of attacks is reduced by depression of nerve transmission in the motor cortex.

Mechanism of action

Phensuximide's mechanism of action not understood, but may act in inhibitory neuronal systems that are important in the generation of the three per second rhythm. It's effects may be related to its ability to inhibit depolarization-induced accumulation of cyclic AMP and cyclic GMP in brain tissue.

Absorption

Rapid and complete.

Volume of distribution
Not Available
Protein binding

21%

Metabolism

Hepatic.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Phensuximide.Approved
MefloquineThe therapeutic efficacy of Phensuximide can be decreased when used in combination with Mefloquine.Approved
MianserinThe therapeutic efficacy of Phensuximide can be decreased when used in combination with Mianserin.Approved, Investigational
OrlistatThe serum concentration of Phensuximide can be decreased when it is combined with Orlistat.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Rankin GO, Cressey-Veneziano K, Wang RT, Brown PI: Urinary tract effects of phensuximide in the Sprague-Dawley and Fischer 344 rat. J Appl Toxicol. 1986 Oct;6(5):349-56. [PubMed:3772011]
  2. CHEN G, WESTON JK, BRATTON AC Jr: Anticonvulsant activity and toxicity of phensuximide, methsuximide and ethosuximide. Epilepsia. 1963 Mar;4:66-76. [PubMed:14020499]
  3. Ferrendelli JA, Kinscherf DA: Inhibitory effects of anticonvulsant drugs on cyclic nucleotide accumulation in brain. Ann Neurol. 1979 Jun;5(6):533-8. [PubMed:38736]
External Links
Human Metabolome Database
HMDB14970
KEGG Drug
D00508
KEGG Compound
C07437
PubChem Compound
6839
PubChem Substance
46505695
ChemSpider
6578
ChEBI
8079
ChEMBL
CHEMBL797
PharmGKB
PA164771230
Wikipedia
Phensuximide
ATC Codes
N03AD02 — Phensuximide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Parke davis div warner lambert co
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)72 °CPhysProp
water solubility7020 mg/LNot Available
logP0.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.21 mg/mLALOGPS
logP0.61ALOGPS
logP0.91ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)19.4ChemAxon
pKa (Strongest Basic)-7.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area37.38 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity51.85 m3·mol-1ChemAxon
Polarizability19.66 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+0.9975
Caco-2 permeable+0.7241
P-glycoprotein substrateNon-substrate0.7832
P-glycoprotein inhibitor INon-inhibitor0.8907
P-glycoprotein inhibitor IINon-inhibitor0.9756
Renal organic cation transporterNon-inhibitor0.7072
CYP450 2C9 substrateNon-substrate0.7511
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9225
CYP450 2D6 inhibitorNon-inhibitor0.9251
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9805
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9612
Ames testNon AMES toxic0.9173
CarcinogenicityNon-carcinogens0.8879
BiodegradationReady biodegradable0.5277
Rat acute toxicity2.0330 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.981
hERG inhibition (predictor II)Non-inhibitor0.9646
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.49 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0udi-3900000000-3ea0132a234fd8153646
GC-MS Spectrum - EI-BGC-MSsplash10-0udi-3900000000-ebb2c45214a57c99d4f6
GC-MS Spectrum - CI-BGC-MSsplash10-0006-0910000000-f0d2f8c20e993a067c81
GC-MS Spectrum - CI-BGC-MSsplash10-000i-0910000000-4a3cc5eeab3149bc14fb
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

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
pyrrolidines (CHEBI:8079)

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
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]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:43