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Identification
NameLacosamide
Accession NumberDB06218
TypeSmall Molecule
GroupsApproved
Description

Lacosamide is a functionalized amino acid that has activity in the maximal electroshock seizure test, and is indicated for the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain. Recent studies indicate that Lacosamide only affects those neurons which are depolarized or active for long periods of time, typical of neurons at the focus of an epileptic seizure, as opposed to other antiepileptic drugs such as carbamazepine or lamotrigine which slow the recovery from inactivation and reduce the ability of neurons to fire action potentials.

Structure
Thumb
Synonyms
Erlosamide
Harkoseride
SPM 927
Vimpat
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Vimpattablet50 mgoralUcb Canada Inc2010-10-21Not applicableCanada
Vimpatinjection10 mg/mLintravenousUCB, Inc.2009-05-26Not applicableUs
Vimpattablet, film coated50 mg/1oralPhysicians Total Care, Inc.2009-10-22Not applicableUs
Vimpatsolution10 mg/mLoralUCB, Inc.2010-04-20Not applicableUs
Vimpattablet, film coated200 mg/1oralUCB, Inc.2009-05-26Not applicableUs
Vimpatsolution10 mgintravenousUcb Canada Inc2011-09-20Not applicableCanada
Vimpattablet, film coated150 mg/1oralUCB, Inc.2009-05-26Not applicableUs
Vimpattablet200 mgoralUcb Canada Inc2010-10-21Not applicableCanada
Vimpattablet, film coated100 mg/1oralUCB, Inc.2009-05-26Not applicableUs
Vimpattablet150 mgoralUcb Canada Inc2010-10-21Not applicableCanada
Vimpattablet, film coated50 mg/1oralUCB, Inc.2009-05-26Not applicableUs
Vimpattablet100 mgoralUcb Canada Inc2010-10-21Not applicableCanada
VimpatkitUCB, Inc.2009-05-26Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII563KS2PQY5
CAS number175481-36-4
WeightAverage: 250.2936
Monoisotopic: 250.131742452
Chemical FormulaC13H18N2O3
InChI KeyInChIKey=VPPJLAIAVCUEMN-GFCCVEGCSA-N
InChI
InChI=1S/C13H18N2O3/c1-10(16)15-12(9-18-2)13(17)14-8-11-6-4-3-5-7-11/h3-7,12H,8-9H2,1-2H3,(H,14,17)(H,15,16)/t12-/m1/s1
IUPAC Name
(2R)-N-benzyl-2-acetamido-3-methoxypropanamide
SMILES
COC[C@@H](NC(C)=O)C(=O)NCC1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentN-acyl-alpha amino acids and derivatives
Alternative Parents
Substituents
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • Phenylmethylamine
  • Benzylamine
  • Benzenoid
  • Monocyclic benzene moiety
  • Acetamide
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Ether
  • Dialkyl ether
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationLacosamide is indicated for adjunctive therapy for partial onset seizures in patients with epilepsy over 17 years old. Injection is indicated for short term use when oral therapy is not feasible.
PharmacodynamicsLacosamide therapy is correlated with a decrease in seizure frequency. It should be noted that in group analyses, dosages above 400 mg/day do not appear to result in additional benefit.
Mechanism of actionIt is proposed that lacosamide's inhibition of sodium channels is responsible for analgesia. Lacosamide may be selective for inhibiting depolarized neurons rather than neurons with normal resting potentials. Pain and nociceptor hyperexcitability are associated with neural membrane depolarization. Lacosamide binds to collapsin response mediator protein-2 (CRMP-2), a phosphoprotein which is expressed primarily in the nervous system and is involved in neuronal differentiation and control of axonal outgrowth. The role CRMP-2 of binding in seizure control is hasn't been elucidated.
Related Articles
AbsorptionLacosamide has a negligible first pass effect with bioavailability of about 100%. The maximum Lacosamide plasma concentrations occur about 1-4 hours after oral administration, and the pharmacokinetics of Lacosamide are dose proportional. Food does not affect absorption.
Volume of distribution

approximately 0.6 L/kg; thus close to the volume of total body water.

Protein binding<15%
Metabolism

Lacosamide is a CYP2C19 substrate. The relative contribution of other CYP isoforms or non-CYP enzymes in the metabolism of lacosamide is not known. Primary compounds excreted were unchanged lacosamide (approximately 40% of the dose), its O-desmethyl metabolite (approximately 30%), and a structurally unknown polar fraction (~20%). The plasma exposure of the major human metabolite, O-desmethyl-lacosamide, is approximately 10% of that of lacosamide. This metabolite has no known pharmacological activity.

SubstrateEnzymesProduct
Lacosamide
Not Available
O-Desmethyl-lacosamideDetails
Route of eliminationLacosamide is eliminated primarily from the systemic circulation by biotransformation and renal excretion.
Half life13 Hours
Clearance

95% recovered in the urine
0.5% in the feces

ToxicityNot Available
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+0.9771
Blood Brain Barrier+0.7181
Caco-2 permeable-0.6886
P-glycoprotein substrateSubstrate0.7158
P-glycoprotein inhibitor INon-inhibitor0.6904
P-glycoprotein inhibitor IINon-inhibitor0.8878
Renal organic cation transporterNon-inhibitor0.8757
CYP450 2C9 substrateNon-substrate0.8732
CYP450 2D6 substrateNon-substrate0.7634
CYP450 3A4 substrateNon-substrate0.6572
CYP450 1A2 substrateNon-inhibitor0.8084
CYP450 2C9 inhibitorNon-inhibitor0.8704
CYP450 2D6 inhibitorNon-inhibitor0.8775
CYP450 2C19 inhibitorNon-inhibitor0.8201
CYP450 3A4 inhibitorNon-inhibitor0.837
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9732
Ames testNon AMES toxic0.7694
CarcinogenicityNon-carcinogens0.8388
BiodegradationNot ready biodegradable0.8499
Rat acute toxicity2.1629 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9678
hERG inhibition (predictor II)Non-inhibitor0.8489
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injectionintravenous10 mg/mL
Kit
Solutionintravenous10 mg
Solutionoral10 mg/mL
Tabletoral100 mg
Tabletoral150 mg
Tabletoral200 mg
Tabletoral50 mg
Tablet, film coatedoral100 mg/1
Tablet, film coatedoral150 mg/1
Tablet, film coatedoral200 mg/1
Tablet, film coatedoral50 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5654301 No1994-08-052014-08-05Us
USRE38551 No2002-03-172022-03-17Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point140-146˚Chttp://www.ema.europa.eu/docs/en_GB/document_library/Application_withdrawal_assessment_report/2010/01/WC500064326.pdf
boiling point536.447 °C at 760 mmHgACD/Labs
water solubilityLacosamide is a white to light yellow powder. It is sparingly soluble in water and slightly soluble in acetonitrile and ethanol.FDA Label
logP0.728ACD/Labs
Predicted Properties
PropertyValueSource
Water Solubility0.465 mg/mLALOGPS
logP0.18ALOGPS
logP-0.022ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)12.47ChemAxon
pKa (Strongest Basic)-1.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area67.43 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity67.57 m3·mol-1ChemAxon
Polarizability26.68 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (18.4 KB)
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
References
Synthesis Reference

http://www.google.com/patents?id=IIanAAAAEBAJ&pg=PA2&source=gbs_selected_pages&cad=3#v=onepage&q&f=false

General References
  1. Sheets PL, Heers C, Stoehr T, Cummins TR: Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine. J Pharmacol Exp Ther. 2008 Jul;326(1):89-99. doi: 10.1124/jpet.107.133413. Epub 2008 Mar 31. [PubMed:18378801 ]
  2. Jones GL, Popli GS, Silvia MT: Lacosamide-induced valproic acid toxicity. Pediatr Neurol. 2013 Apr;48(4):308-10. doi: 10.1016/j.pediatrneurol.2012.12.039. [PubMed:23498565 ]
External Links
ATC CodesN03AX18
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (276 KB)
MSDSDownload (570 KB)
Interactions
Drug Interactions
Drug
AcebutololAcebutolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
AmiodaroneAmiodarone may increase the atrioventricular blocking (AV block) activities of Lacosamide.
AtazanavirThe serum concentration of Lacosamide can be increased when it is combined with Atazanavir.
AtenololAtenolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
BeractantBeractant may increase the atrioventricular blocking (AV block) activities of Lacosamide.
BetaxololBetaxolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
BisoprololBisoprolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
BoceprevirThe serum concentration of Lacosamide can be increased when it is combined with Boceprevir.
CalfactantCalfactant may increase the atrioventricular blocking (AV block) activities of Lacosamide.
CapecitabineThe serum concentration of Lacosamide can be increased when it is combined with Capecitabine.
CarbamazepineCarbamazepine may increase the atrioventricular blocking (AV block) activities of Lacosamide.
CarteololCarteolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
CarvedilolCarvedilol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
CeritinibThe serum concentration of Lacosamide can be increased when it is combined with Ceritinib.
ClarithromycinThe serum concentration of Lacosamide can be increased when it is combined with Clarithromycin.
ClonidineClonidine may increase the atrioventricular blocking (AV block) activities of Lacosamide.
CobicistatThe serum concentration of Lacosamide can be increased when it is combined with Cobicistat.
CrizotinibCrizotinib may increase the atrioventricular blocking (AV block) activities of Lacosamide.
DarunavirThe serum concentration of Lacosamide can be increased when it is combined with Darunavir.
DelavirdineThe serum concentration of Lacosamide can be increased when it is combined with Delavirdine.
DexmedetomidineDexmedetomidine may increase the atrioventricular blocking (AV block) activities of Lacosamide.
DigoxinDigoxin may increase the atrioventricular blocking (AV block) activities of Lacosamide.
DiltiazemDiltiazem may increase the atrioventricular blocking (AV block) activities of Lacosamide.
DonepezilDonepezil may increase the atrioventricular blocking (AV block) activities of Lacosamide.
DronedaroneDronedarone may increase the atrioventricular blocking (AV block) activities of Lacosamide.
EsmololEsmolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
FingolimodFingolimod may increase the atrioventricular blocking (AV block) activities of Lacosamide.
FloxuridineThe serum concentration of Lacosamide can be increased when it is combined with Floxuridine.
FluorouracilThe serum concentration of Lacosamide can be increased when it is combined with Fluorouracil.
FosphenytoinThe serum concentration of Lacosamide can be decreased when it is combined with Fosphenytoin.
GalantamineGalantamine may increase the atrioventricular blocking (AV block) activities of Lacosamide.
GemfibrozilThe serum concentration of Lacosamide can be increased when it is combined with Gemfibrozil.
GuanfacineGuanfacine may increase the atrioventricular blocking (AV block) activities of Lacosamide.
IdelalisibThe serum concentration of Lacosamide can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Lacosamide can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Lacosamide can be increased when it is combined with Itraconazole.
IvabradineIvabradine may increase the atrioventricular blocking (AV block) activities of Lacosamide.
KetoconazoleThe serum concentration of Lacosamide can be increased when it is combined with Ketoconazole.
LabetalolLabetalol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
LanreotideLanreotide may increase the atrioventricular blocking (AV block) activities of Lacosamide.
LevobunololLevobunolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
LucinactantLucinactant may increase the atrioventricular blocking (AV block) activities of Lacosamide.
MefloquineThe therapeutic efficacy of Lacosamide can be decreased when used in combination with Mefloquine.
MethyldopaMethyldopa may increase the atrioventricular blocking (AV block) activities of Lacosamide.
MetipranololMetipranolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
MetoprololMetoprolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
MianserinThe therapeutic efficacy of Lacosamide can be decreased when used in combination with Mianserin.
NadololNadolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
NebivololNebivolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
NefazodoneThe serum concentration of Lacosamide can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Lacosamide can be increased when it is combined with Nelfinavir.
NicardipineThe serum concentration of Lacosamide can be increased when it is combined with Nicardipine.
OctreotideOctreotide may increase the atrioventricular blocking (AV block) activities of Lacosamide.
OrlistatThe serum concentration of Lacosamide can be decreased when it is combined with Orlistat.
PasireotidePasireotide may increase the atrioventricular blocking (AV block) activities of Lacosamide.
PenbutololPenbutolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
PhenobarbitalThe serum concentration of Lacosamide can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Lacosamide can be decreased when it is combined with Phenytoin.
PindololPindolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
Poractant alfaPoractant alfa may increase the atrioventricular blocking (AV block) activities of Lacosamide.
PosaconazoleThe serum concentration of Lacosamide can be increased when it is combined with Posaconazole.
PropafenonePropafenone may increase the atrioventricular blocking (AV block) activities of Lacosamide.
PropranololPropranolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
RitonavirThe serum concentration of Lacosamide can be increased when it is combined with Ritonavir.
RivastigmineRivastigmine may increase the atrioventricular blocking (AV block) activities of Lacosamide.
SaquinavirThe serum concentration of Lacosamide can be increased when it is combined with Saquinavir.
SotalolSotalol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
SufentanilSufentanil may increase the atrioventricular blocking (AV block) activities of Lacosamide.
SulfadiazineThe serum concentration of Lacosamide can be increased when it is combined with Sulfadiazine.
SulfisoxazoleThe serum concentration of Lacosamide can be increased when it is combined with Sulfisoxazole.
TelaprevirThe serum concentration of Lacosamide can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Lacosamide can be increased when it is combined with Telithromycin.
TimololTimolol may increase the atrioventricular blocking (AV block) activities of Lacosamide.
TizanidineTizanidine may increase the atrioventricular blocking (AV block) activities of Lacosamide.
TolbutamideThe serum concentration of Lacosamide can be increased when it is combined with Tolbutamide.
VerapamilVerapamil may increase the atrioventricular blocking (AV block) activities of Lacosamide.
VoriconazoleThe serum concentration of Lacosamide can be increased when it is combined with Voriconazole.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
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 sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, es...
Gene Name:
SCN9A
Uniprot ID:
Q15858
Molecular Weight:
226370.175 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN3A
Uniprot ID:
Q9NY46
Molecular Weight:
226291.905 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated sodium channel activity
Specific Function:
Tetrodotoxin-resistant channel that 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 sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
Gene Name:
SCN10A
Uniprot ID:
Q9Y5Y9
Molecular Weight:
220623.605 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
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Drug created on March 19, 2008 10:17 / Updated on June 28, 2016 01:52