Phenacemide

Identification

Name
Phenacemide
Accession Number
DB01121  (APRD00089)
Type
Small Molecule
Groups
Approved
Description

Phenacemide is used to control certain seizures in the treatment of epilepsy. This medicine acts on the central nervous system (CNS) to reduce the number and severity of seizures.

Structure
Thumb
Synonyms
Not Available
External IDs
Not Available
Product Ingredients
Not Available
Approved Prescription Products
Not Available
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Phenurone
Brand mixtures
Not Available
Categories
UNII
PAI7J52V09
CAS number
63-98-9
Weight
Average: 178.1879
Monoisotopic: 178.074227574
Chemical Formula
C9H10N2O2
InChI Key
XPFRXWCVYUEORT-UHFFFAOYSA-N
InChI
InChI=1S/C9H10N2O2/c10-9(13)11-8(12)6-7-4-2-1-3-5-7/h1-5H,6H2,(H3,10,11,12,13)
IUPAC Name
(2-phenylacetyl)urea
SMILES
NC(=O)NC(=O)CC1=CC=CC=C1

Pharmacology

Indication

Used to control certain seizures in the treatment of epilepsy.

Structured Indications
Not Available
Pharmacodynamics

Phenacemide is a ureal anticonvulsant indicated for control of severe epilepsy, particularly mixed forms of complex partial (psychomotor or temporal lobe) seizures, refractory to other anticonvulsants. Phenacemide elevates the threshold for minimal electroshock convulsions and abolishes the tonic phase of maximal electroshock seizures. It also prevents or modifies seizures induced by pentylenetetrazol or other convulsants.

Mechanism of action

Phenacemide binds to and blocks neuronal sodium channels or voltage sensitive calcium channels. This blocks or suppresses neuronal depolarization and hypersynchronization. Hypersynchronization is what often causes seizures.

TargetActionsOrganism
ASodium channel protein type 1 subunit alpha
inhibitor
Human
Absorption

Almost completely absorbed.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolized in the liver by hepatic microsomal enzymes, where it is inactivated by p-hydroxylation.

Route of elimination
Not Available
Half life

22-25 hours.

Clearance
Not Available
Toxicity

Oral, mouse: LD50 = 987 mg/kg; Oral, rabbit: LD50 = 2500 mg/kg; Oral, rat: LD50 = 1600 mg/kg

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
MefloquineThe therapeutic efficacy of Phenacemide can be decreased when used in combination with Mefloquine.Approved
MianserinThe therapeutic efficacy of Phenacemide can be decreased when used in combination with Mianserin.Approved
OrlistatThe serum concentration of Phenacemide can be decreased when it is combined with Orlistat.Approved, Investigational
Food Interactions
  • May be taken with food if stomach upset occurs.

References

Synthesis Reference
Not Available
General References
  1. Coker SB: The use of phenacemide for intractable partial complex epilepsy in children. Pediatr Neurol. 1986 Jul-Aug;2(4):230-2. [PubMed:3508693 ]
  2. Coker SB, Holmes EW, Egel RT: Phenacemide therapy of complex partial epilepsy in children: determination of plasma drug concentrations. Neurology. 1987 Dec;37(12):1861-6. [PubMed:3683877 ]
External Links
Human Metabolome Database
HMDB15253
KEGG Drug
D00504
KEGG Compound
C07428
PubChem Compound
4753
PubChem Substance
46508400
ChemSpider
4589
ChEBI
8049
ChEMBL
CHEMBL918
Therapeutic Targets Database
DAP000501
PharmGKB
PA164745309
Wikipedia
Phenacemide
ATC Codes
N03AX07 — Phenacemide
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Download (72.7 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)215 °CPhysProp
water solubility10.2 g/LNot Available
logP0.87HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility1.06 mg/mLALOGPS
logP0.81ALOGPS
logP0.46ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)11.75ChemAxon
pKa (Strongest Basic)-7.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area72.19 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity47.43 m3·mol-1ChemAxon
Polarizability17.49 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9401
Blood Brain Barrier+0.9935
Caco-2 permeable-0.6496
P-glycoprotein substrateNon-substrate0.7351
P-glycoprotein inhibitor INon-inhibitor0.9376
P-glycoprotein inhibitor IINon-inhibitor0.9913
Renal organic cation transporterNon-inhibitor0.8761
CYP450 2C9 substrateNon-substrate0.7678
CYP450 2D6 substrateNon-substrate0.7784
CYP450 3A4 substrateNon-substrate0.8055
CYP450 1A2 substrateNon-inhibitor0.7929
CYP450 2C9 inhibitorNon-inhibitor0.8962
CYP450 2D6 inhibitorNon-inhibitor0.942
CYP450 2C19 inhibitorNon-inhibitor0.9183
CYP450 3A4 inhibitorNon-inhibitor0.9088
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9183
Ames testNon AMES toxic0.8748
CarcinogenicityNon-carcinogens0.799
BiodegradationReady biodegradable0.8039
Rat acute toxicity2.0779 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9546
hERG inhibition (predictor II)Non-inhibitor0.9759
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
Predicted LC-MS/MS Spectrum - 10V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 10V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, NegativePredicted LC-MS/MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-00kf-9200000000-38554ddfe2ad3808dc2a
1H NMR Spectrum1D NMRNot applicable

Taxonomy

Description
This compound belongs to the class of chemical entities known as phenylacetamides. These are amide derivatives of phenylacetic acids.
Kingdom
Chemical entities
Super Class
Organic compounds
Class
Benzenoids
Sub Class
Benzene and substituted derivatives
Direct Parent
Phenylacetamides
Alternative Parents
N-acyl ureas / Dicarboximides / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Phenylacetamide / N-acyl urea / Ureide / Dicarboximide / Carbonic acid derivative / Urea / Carboxylic acid derivative / Organopnictogen compound / Carbonyl group / Organooxygen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
acetamides (CHEBI:8049 )

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity
Specific Function
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a...
Gene Name
SCN1A
Uniprot ID
P35498
Uniprot Name
Sodium channel protein type 1 subunit alpha
Molecular Weight
228969.49 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Wong MG, Defina JA, Andrews PR: Conformational analysis of clinically active anticonvulsant drugs. J Med Chem. 1986 Apr;29(4):562-72. [PubMed:3959032 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Drug created on June 13, 2005 07:24 / Updated on September 01, 2017 10:36