Lacosamide  

Lacosamide
Systematic (IUPAC) name
N2-acetyl-N-benzyl-D-homoserinamide
Identifiers
CAS number	175481-36-4
ATC code	N03AX18
PubChem	219078
Chemical data
Formula	C13H18N2O3
Mol. mass	250.294 g/mol
Synonyms	(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide
Pharmacokinetic data
Bioavailability	High
Metabolism	?
Half life	13 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status	Schedule V (U.S.)
Routes	Oral, intravenous

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 acts by enhancing slow inactivation of voltage gated sodium channels^[7] . 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.^[7]

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 ^[8]

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.^[9] In a smaller trial of people with diabetic neuropathy, lacosamide also provided significantly better pain relief when compared to placebo.^[10]

References