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<!--Clinical data-->
<!--Clinical data-->
| tradename =
| tradename = Vimpat
| Drugs.com = {{drugs.com|monograph|lacosamide}}
| Drugs.com = {{drugs.com|monograph|lacosamide}}
| MedlinePlus = a609028
| MedlinePlus = a609028

Revision as of 17:35, 4 January 2012

Lacosamide
Clinical data
Trade namesVimpat
Other names(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide
AHFS/Drugs.comMonograph
MedlinePlusa609028
Routes of
administration		Oral, intravenous
ATC code
Legal status
Legal status
  • Schedule V (U.S.)
Pharmacokinetic data
BioavailabilityHigh
Elimination half-life13 hours
Identifiers
  • N2-acetyl-N-benzyl-D-homoserinamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.112.805 Edit this at Wikidata
Chemical and physical data
FormulaC13H18N2O3
Molar mass250.294 g/mol g·mol−1
3D model (JSmol)
  • O=C(N[C@@H](C(=O)NCc1ccccc1)COC)C
  • 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 checkY
  • Key:VPPJLAIAVCUEMN-GFCCVEGCSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Lacosamide (INN, formerly known as erlosamide) is a medication developed by UCB for the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain marketed under the trade name Vimpat.

The U.S. Food and Drug Administration accepted UCB's New Drug Application for lacosamide as of November 29, 2007, beginning the approval process for the drug.[1][2] UCB also filed for marketing approval in the European Union; the European Medicines Agency accepted the marketing application for review in May 2007.[1][3]

The drug was approved in the EU on September 3, 2008.[4] It was approved in the US on October 29, 2008.[5] Lacosamide release was delayed owing to an objection about its placement into schedule V of the Controlled Substances Act. The FDA issued their final rule of placement into Schedule V on June 22, 2009[6].

Mechanism of action

Lacosamide is a functionalized amino acid that has activity in the maximal electroshock seizure test, like antiepileptic drugs that are believed to act through voltage-gated sodium channels[7]. However, lacosamide does not act in a conventional way to stabilize fast sodium channel inactivation. Rather, recent studies indicate that it enhances slow inactivation[8] . During an action potential voltage gated sodium channels undergo fast inactivation. This inactivation prevents the channel from opening, and helps end the action potential. Many antiepileptic drugs, like carbamazepine or lamotrigine, slow the recovery from inactivation and hence reduce the ability of neurons to fire action potentials. Inactivation only occurs in neurons firing action potentials, this means that drugs that modulate fast inactivation selectively reduce the firing in active cells. Slow inactivation is similar but does not produce complete blockade of voltage gated sodium channels, with both activation and inactivation occurring over hundreds of milliseconds or more. Lacosamide makes this inactivation happen at less depolarized membrane potentials. This means that lacosamide only effects neurons which are depolarized or active for long periods of time, typical of neurons at the focus of an epileptic focus.[8]

Lacosamide does not affect AMPA, kainate, NMDA, GABAA, GABAB or a variety of dopaminergic, serotonergic, adrenergic, muscarinic or cannabinoid receptors and does not block potassium or calcium currents [9]

Clinical trials

In a large double-blind, randomized clinical trial of people with poorly controlled partial-onset seizures, lacosamide was found to significantly reduce seizure frequency when given in addition to other antiepileptics, at doses of 400 and 600 milligrams a day.[10] In a smaller trial of people with diabetic neuropathy, lacosamide also provided significantly better pain relief when compared to placebo.[11]

Tolerability

Lacosamide was generally well tolerated in adult patients with partial-onset seizures. Dizziness was the most common treatment-related adverse event.[12]

Chemistry

J.A. McIntyre, J. Castaner, Drugs Future 29, 992 (2004).

References

  1. ^ a b "UCB Announces FDA Filing for lacosamide in the Treatment of Diabetic Neuropathic Pain" (Press release). UCB. 2007-11-29. Retrieved 2007-11-29.
  2. ^ "UCB Announces FDA Filing for lacosamide in the Treatment of Partial Onset Seizures in Adults with Epilepsy" (Press release). UCB. 2007-11-29. Retrieved 2007-11-29.
  3. ^ Wan, Yuet (August 17, 2007). "Marketing application for lacosamide (Vimpat) filed in EU for treatment of diabetic neuropathic pain". PharmaTimes through the UK National electronic Library for Medicines. Retrieved 2007-11-30. {{cite news}}: Italic or bold markup not allowed in: |publisher= (help) [dead link‍]
  4. ^ "Vimpat Approved in Europe" (Press release). UCB. 2008-09-03. Retrieved 2008-09-17.
  5. ^ "UCB's Vimpat approved by U.S. FDA as adjunctive therapy for partial onset seizures in adults" (Press release). UCB. 2008-10-29. Retrieved 2008-11-25.
  6. ^ "FDA places lacosamide in Schedule V" (Press release). FDA. 2009-06-22. Retrieved 2009-06-28.
  7. ^ Rogawski MA (2006). "Diverse mechanisms of antiepileptic drugs in the development pipeline". Epilepsy Res. 69 (3): 273–94. doi:10.1016/j.eplepsyres.2006.02.004. PMC 1562526. PMID 16621450. {{cite journal}}: Unknown parameter |month= ignored (help)
  8. ^ a b Errington AC, Stöhr T, Heers C, Lees G (2008). "The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels". Molecular pharmacology. 73 (1): 157–69. doi:10.1124/mol.107.039867. PMID 17940193. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Errington AC, Coyne L, Stöhr T, Selve N, Lees G (2006). "Seeking a mechanism of action for the novel anticonvulsant lacosamide". Neuropharmacology. 50 (8): 1016–29. doi:10.1016/j.neuropharm.2006.02.002. PMID 16620882. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD (2007). "Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures". Epilepsia. 48 (7): 1308–17. doi:10.1111/j.1528-1167.2007.01188.x. PMID 17635557.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Rauck RL, Shaibani A, Biton V, Simpson J, Koch B (2007). "Lacosamide in painful diabetic peripheral neuropathy: a phase 2 double-blind placebo-controlled study". Clin J Pain. 23 (2): 150–8. doi:10.1097/01.ajp.0000210957.39621.b2. PMID 17237664.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ Cross SA, Curran MP.[1].Drugs 2009;69(4):449-459.doi: 10.2165/00003495-200969040-00005.
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