Lacosamide

Lacosamide

File:Lacosamide.svg
Systematic (IUPAC) name
N2-acetyl-N-benzyl-D-homoserinamide
Clinical data
Routes of administration	Oral, intravenous
Legal status
Legal status	Schedule V (U.S.)
Pharmacokinetic data
Bioavailability	High
Biological half-life	13 hours
Identifiers
CAS Number	175481-36-4
ATC code	N03AX18 (WHO)
PubChem	CID 219078
Synonyms	(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide
Chemical data
Formula	C13H18N2O3
Molar mass	250.294 g/mol[[]]

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. UCB also filed for marketing approval in the European Union; the European Medicines Agency accepted the marketing application for review in May 2007.

The drug was approved in the EU on September 3, 2008. It was approved in the US on October 29, 2008. 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.

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. However, lacosamide does not act in a conventional way to stabilize fast sodium channel inactivation. Rather, recent studies indicate that it enhances slow inactivation . Voltage gated sodium channels are the membrane proteins responsible for generating the neuronal action potential, the all or none electrical event which causes neurons to release neurotransmitter. During an action potential voltage gated sodium channels undergo fast inactivation, a process which takes a few milliseconds. This inactivation prevents the channel from opening, and helps end the action potential. Many typical antiepileptic drugs, like carbamazepine or lamotrigine, slow the recovery from inactivation and hence reduce the ability of neurons to fire action potentials. As inactivation only occurs in neurons firing action potentials, this means that drug that modulate fast inactivation selectively reduce the firing in active cells.

Slow inactivation is a similar processes, except that it does not produce complete blockade of voltage gated sodium channels, and it occurs over the course of hundreds of milliseconds or more, and recovery from this state takes equally as long. 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.

Lacosamide does not affect AMPA, kainate, NMDA, GABA_A, GABA_B or a variety of dopaminergic, serotonergic, adrenergic, muscarinic or cannabinoid receptors and does not block potassium or calcium currents

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. In a smaller trial of people with diabetic neuropathy, lacosamide also provided significantly better pain relief when compared to placebo.

Tolerability

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

Chem

500px

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

References

de:Lacosamid pt:Lacosamida