Lacosamide

DescriptionLacosamide (LCM), (SPM 927, (R)-2-acetamido-N-benzyl-3-methoxypropionamide, previously referred to as harkoseride or ADD 234037) is a member of a series of functionalized amino acids that were specifically synthesized as anticonvulsant or antiepileptic drug. It reduces the spread of seizure activity in the brain. Lacosamide appears to have a dual mode of action: selective enhancement of sodium channel inactivation and modulation of collapsin response mediator protein-2. Compared to novel antiepileptic drugs, lacosamide has broader and higher efficacy, better tolerability, and improved pharmacokinetic properties. Lacosamide is in phase III clinical development for adjunctive treatment of patients with uncontrolled partial-onset seizures, and for monotherapy of patients with painful diabetic neuropathy. It is absorbed rapidly and completely after oral administration. Lacosamide has an elimination half-life of approximately 13 hours and a low potential for drug interactions. Additionally, lacosamide exhibits linear, dose-proportional pharmacokinetics with low intra- and interpatient variability. Lacosamide (licensed in 2008) is a third- generation AED known with the proprietary brand name of Vimpat® (UCB Pharma, Slough) in the UK and USA.

UsesLacosamide is an anticonvulsant and analgesic compound used for the treatment of partial-onset seizures and neuropathic pain. It can also used for the treatment of status epilepticus. Its analgesic effect is mediated by its inhibitory effect on sodium channels, which leads to neural membrane depolarization. Its interaction with the collapsin-response mediator protein 2 (CRMP-2 alias DRP-2) may also facilitate the above process, although the detailed mechanism remains to be elucidated.

DescriptionAlthough epilepsy is a neurological disorder with varying etiology and severity, the common feature is unprovoked, recurring seizures. Whether classified as generalized, involving both cerebral hemispheres, or partial with only localized portions of brain participation at onset, effective treatment relies on accurate assessment of syndrome type to optimally decrease the frequency, duration, and severity of seizures. The latest weapon against partial onset epilepsy is lacosamide, formerly known as harkoseride and erlosamide. The data also indicate that lacosamide binds to collapsing response mediator protein 2 (CRMP2); CRMP2 is involved in neuronal differentiation, control of axonal outgrowth, and possibly epileptogenesis. Furthermore, lacosamide is heralded as having a dual mode of action as it has also displayed efficacy against diabetic neuropathy, possibly as a result of stabilization of neuronal hyperexcitability. Currently,lacosamide is approved as adjunctive treatment of partial onset seizures in patients 17 years or older and is in development as a monotherapy for epilepsy and for neuropathic pain.

DescriptionLacosamide selectively enhances sodium channel slow inactivation without affecting fast inactivation. It is effective in multiple rodent models of seizure activity. The neuroprotective effects of lacosamide are also attributed to its ability to modulate collapsin response mediator protein 2 (CRMP-2), a member of the semaphorin signal transduction pathway. Formulations containing lacosamide have been used as an adjunctive or monotherapy for focal-onset seizures but, at higher doses, have a low potential for abuse. Lacosamide is regulated as a Schedule V compound in the United States.

HistoryLacosamide, a functionalized amino acid, has become an important third-generation antiepileptic drug after systematic drug development. Its discovery stemmed from a 1996 study at the University of Houston, where researchers hypothesized that modified amino acids might have potential applications in epilepsy treatment. Against this backdrop, Dr. Harold Cohen and his team, while studying the mechanism of action of biotin, noticed its structural similarity to certain neuroactive compounds, inspiring them to synthesize a series of functionalized amino acids and screen for their anticonvulsant activity. With the support of the National Institute of Neurological Diseases and Stroke (NINDS) anticonvulsant drug screening program, lacosamide (then codenamed SPM 927) was identified as a promising candidate drug due to its potent anticonvulsant properties.In 2000, Schwarz Pharma in Germany collaborated with Harris FRC to advance the preclinical and clinical development of lacosamide. Based on substantial clinical evidence, lacosamide's marketing application was approved by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) in 2007. In September 2008, the drug was officially approved for marketing in the European Union, and in October of the same year, it was approved in the United States under the brand name Vimpat®. In November 2018, lacosamide tablets were approved for marketing in China, becoming the first third-generation antiepileptic drug approved in China. Subsequently, oral solutions and other dosage forms were also launched. To date, the clinical application of lacosamide has expanded from its initial role as adjunctive therapy for adult partial epilepsy to monotherapy, and is used to treat a wider range of pediatric patients and primary generalized tonic-clonic epilepsy.

UsesA potent anticonvulsant.