Lacosamide
Encyclopedia
Lacosamide is a medication developed by UCB
for the adjunctive treatment of partial-onset seizure
s 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.
. 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 potential
s. 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
, GABAA, GABAB
or a variety of dopaminergic, serotonergic, adrenergic, muscarinic or cannabinoid receptors and does not block potassium or calcium currents
, 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
.
UCB (company)
UCB is a multinational biopharmaceutical manufacturing company headquartered in Brussels, Belgium.- History :UCB was founded on 18 January 1928 by Emmanuel Janssen, a Belgian businessman...
for the adjunctive treatment of partial-onset seizure
Focal seizures
Partial seizures are seizures which affect only a part of the brain at onset. The brain is divided into two hemispheres, each consisting of four lobes - the frontal, temporal, parietal and occipital lobes...
s and diabetic neuropathic pain
Diabetic neuropathy
Diabetic neuropathies are neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves in addition to macrovascular conditions that can culminate in diabetic neuropathy...
marketed under the trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....
Vimpat.
The U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
accepted UCB's New Drug Application
New drug application
The New Drug Application is the vehicle in the United States through which drug sponsors formally propose that the Food and Drug Administration approve a new pharmaceutical for sale and marketing...
for lacosamide as of November 29, 2007, beginning the approval process for the drug. UCB also filed for marketing approval in the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
; the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
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
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
. 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. 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
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
or lamotrigine
Lamotrigine
Lamotrigine, marketed in the US and most of Europe as Lamictal by GlaxoSmithKline, is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. It is also used as an adjunct in treating depression, though this is considered off-label usage...
, 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 potential
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...
s. 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
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
, kainate
Kainate receptor
Kainate receptors, or KARs, are non-NMDA ionotropic receptors which respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a drug first isolated from red algae Digenea simplex. KARs are less well...
, NMDA
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
, GABAA, GABAB
GABA B receptor
GABAB receptors are metabotropic transmembrane receptors for gamma-aminobutyric acid that are linked via G-proteins to potassium channels...
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-blindDouble-blind
A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....
, randomized
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
of people with poorly controlled partial-onset seizures, lacosamide was found to significantly
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
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
Diabetic neuropathy
Diabetic neuropathies are neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves in addition to macrovascular conditions that can culminate in diabetic neuropathy...
, lacosamide also provided significantly better pain relief
Pain management
Pain management is a branch of medicine employing an interdisciplinary approach for easing the suffering and improving the quality of life of those living with pain. The typical pain management team includes medical practitioners, clinical psychologists, physiotherapists, occupational therapists,...
when compared to placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
.