Lacosamide as treatment for partial epilepsy: Mechanisms of action, pharmacology, effects, and safety

Therapeutics and Clinical Risk Management

Volumn 5, Issue 1, 2009, Pages 757-766

  Kellinghaus, Christoph ^a  

^a Andreas Bannowsky Ltd   (Germany)

Author keywords

Antiepileptic drug; Epilepsy; Lacosamide

Indexed keywords

COLLAPSIN RESPONSE MEDIATOR PROTEIN 2; CYTOCHROME P450; DIAZEPAM; HARKOSERIDE; VOLTAGE GATED SODIUM CHANNEL;

ANALGESIC ACTIVITY; ANTICONVULSANT ACTIVITY; ANXIETY DISORDER; AREA UNDER THE CURVE; ASTHENIA; ATAXIA; ATRIOVENTRICULAR BLOCK; BIOEQUIVALENCE; BLURRED VISION; BODY WEIGHT; BRADYCARDIA; CLINICAL TRIAL; COORDINATION DISORDER; DIPLOPIA; DIZZINESS; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; ERYTHEMA; EUROPEAN UNION; FATIGUE; FOCAL EPILEPSY; GRAND MAL EPILEPSY; HEADACHE; HEART BUNDLE BRANCH BLOCK; HUMAN; HYPESTHESIA; IN VITRO STUDY; NAUSEA; NERVE CELL PLASTICITY; NONHUMAN; NYSTAGMUS; PR INTERVAL; PSYCHOSIS; QT INTERVAL; REVIEW; RHINOPHARYNGITIS; SEIZURE; SIDE EFFECT; SOMNOLENCE; SYNCOPE; TREMOR; UNITED STATES; VERTIGO; VOMITING;

EID: 77949469954     PISSN: 11766336     EISSN: 1178203X     Source Type: Journal    
DOI: 10.2147/tcrm.s5189     Document Type: Review

References (51)

1. Fisher RS, van Emde BW, Blume W, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005;46:470-472.
2. Berg AT. Epidemiologic aspects of Epilepsy. In: Wyllie E, Gupta A, Lachhwani DK (ed). The Treatment of Epilepsy - Principles and Practice. 4th ed., Philadelphia: Lippincott Williams & Wilkins; 2006:109-116.
3. Keränen T, Riekkinen P. Severe epilepsy: diagnostic and epidemiological aspects. Acta Neurol Scand Suppl. 1988;117:7-14.
4. Kwan P,Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342:314-319.
5. Bialer M. New antiepileptic drugs currently in clinical trials: is there a strategy in their development? Ther Drug Monit. 2002;24:85-90.
6. Cortes S, Liao ZK, Watson D, Kohn H. Effect of structural modification of the hydantoin ring on anticonvulsant activity. J Med Chem. 1985;28:601-606.
7. Andurkar SV, Stables JP, Kohn H. The anticonvulsant activities of N-benzyl 3-methoxypropionamides. Bioorg Med Chem. 1999;7:2381-2389.
8. Beyreuther BK, Freitag J, Heers C, et al. Lacosamide: a review of preclinical properties. CNS Drug Rev. 2007;13:21-42.
9. Choi D, Stables JP, Kohn H. Synthesis and anticonvulsant activities of N-benzyl-2-acetamidopropionamide derivatives. J Med Chem. 1996;39:1907-1916.
10. Hovinga CA. SPM-927 (Schwarz Pharma). IDrugs. 2003;6:479-485.
11. LeTiran A, Stables JP, Kohn H. Functionalized amino acid anticonvulsants: synthesis and pharmacological evaluation of conformationally restricted analogues. Bioorg Med Chem. 2001;9:2693-2708.
12. Errington AC, Coyne L, Stöhr T, Selve N, Lees G. Seeking a mechanism of action for the novel anticonvulsant lacosamide. Neuropharmacology. 2006;50:1016-1029.
13. Lees G, Stöhr T, Errington AC. Stereoselective effects of the novel anticonvulsant lacosamide against 4-AP induced epileptiform activity in rat visual cortex in vitro. Neuropharmacology. 2006;50:98-110.
14. Errington AC, Stöhr T, Heers C, Lees G. The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Mol Pharmacol. 2008;73:157-169.
15. Yoshimura T, Kawano Y, Arimura N, et al. GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell. 2005;120:137-149.
16. Czech T, Yang JW, Csaszar E, et al. Reduction of hippocampal collapsin response mediated protein-2 in patients with mesial temporal lobe epilepsy. Neurochem Res. 2004;29:2189-2196.
17. Möddel G, Jacobson B, Ying Z, et al. The NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia. Brain Res. 2005;1046:10-23.
18. Horstmann R, Bonn R, Cawello W, Doty P, Rudd D. Basic clinical pharmacologic investigations of the new antiepileptic drug SPM 927. Epilepsia. 2002;43(Suppl 7):188.
19. Cawello W, Kropeit D, Schiltmeyer B, Hammes W, Horstmann R. Food does not affect the pharmacokinetics of SPM 927. Epilepsia. 2004;45(Suppl 7):307.
20. Thomas D, Scharfenecker U, Nickel B, et al. Low potential for drug-drug interaction of lacosamide. Epilepsia. 2006;47(Suppl 4):200.
21. Schiltmeyer B, Cawello W, Kropeit D, Hammes W, Horstmann R. Pharmacokinetics of the new antiepileptic drug SPM 927 in human subjects with different age and gender. Epilepsia. 2004;45(Suppl 7):313.
22. Cross SA, Curran MP. Lacosamide: in partial-onset seizures. Drugs. 2009;69:449-459.
23. Doty P, Rudd GD, Stoehr T, Thomas D. Lacosamide. Neurotherapeutics. 2007;4:145-148.
24. Horstmann R, Bonn R, Cawello W, Doty P, Rudd D. SPM 927 does not interact with valproic acid and carbamazepine. Epilepsia. 2003;44(Suppl 9):97.
25. Schiltmeyer B, Kropeit D, Cawello W, Hammes W, Horstmann R. No interaction between lacosamide and metformin. J Pain. 2006;7:S63.
26. Ben Menachem E, Biton V, Jatuzis D, et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007;48:1308-1317.
27. Fountain N, French J, Priviteril MD. Harkoseride: safety and tolerability of a new antiepileptic drug (AED) in patients with refracotry partial seizures. Epilepsia. 2000;4 (Suppl 7):169.
28. Halasz P, Kalviainen R, Mazurkiewicz-Beldzinska M, et al. Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trial. Epilepsia. 2009;50:443-453.
29. Bialer M, Johannessen SI, Kupferberg HJ, et al. Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V). Epilepsy Res. 2001;43:11-58.
30. Swinyard EA, Brown WC, Goodman LS. Comparative assays of antiepileptic drugs in mice and rats. J Pharmacol Exp Ther. 1952;106:319-330.
31. Stöhr T, Kupferberg HJ, Stables JP, et al. Lacosamide, a novel anti-convulsant drug, shows efficacy with a wide safety margin in rodent models for epilepsy. Epilepsy Res. 2007;74:147-154.
32. Barton ME, Klein BD, Wolf HH, White HS. Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy. Epilepsy Res. 2001;47:217-227.
33. Duncan GE, Kohn H. The novel antiepileptic drug lacosamide blocks behavioral and brain metabolic manifestations of seizure activity in the 6 Hz psychomotor seizure model. Epilepsy Res. 2005;67:81-87.
34. Lothman EW, Williamson JM. Closely spaced recurrent hippocampal seizures elicit two types of heightened epileptogenesis: a rapidly developing, transient kindling and a slowly developing, enduring kindling. Brain Res. 1994;649:71-84.
35. Sachdeo R, Montouris G, Beydoun A, et al. An open-label, maximum tolerated dose trial to evaluate oral SPM 927 as adjunctive therapy in patients with partial seizures. Neurology. 2003;6(Suppl 1):A433.
36. Chung SS, Sperling M, Biton V, et al. Lacosamide: efficacy and safety as oral adjunctive treatment for partial-onset seizures. Epilepsia. 2007;4(Suppl 6):Poster 3.197.
37. Rosenfeld WE, Montouris G, Whitesides J, Doty P, Rudd D. Long-term safety and efficacy of SPM 927 as adjunctive therapy in subjects with partial seizures: 24-week follow-up. Epilepsia. 2003;4(Suppl 9):262.
38. Shaibani A, Fares S, Selam JL, et al. Lacosamide in painful diabetic neuropathy: an 18-week double-blind placebo-controlled trial. J Pain. 2009;
39. Wymer JP, Simpson J, Sen D, Bongardt S. Efficacy and safety of lacosamide in diabetic neuropathic pain: an 18-week double-blind placebo-controlled trial of fixed-dose regimens. Clin J Pain. 2009;25:376-385.
40. Ziegler D, Bongardt S, Koc B, Thierfelder S. Efficacy and safety of Lacosamide in the treatment of neuropahtic pain attributed to distal diabetic neuropathy. Epilepsia. 2005;46(Suppl 8):187.
41. Graf R, Frye W, Simpson J, Jay G. Lacosamide in long-term treatment of painful diabetic neuropathy (DNP). Eur J Neurol. 2007;14(Suppl 1):260.
42. Rosenfeld W, Fountain N, Kaubrys G, Heinzen L, McShea C. Lacosamide: an interim evaluation of the long-term safety and efficacy as oral adjunctive therapy in subjects with partial-onset seizures. Epilepsia. 2007;48(Suppl 6):Poster.
43. Cawello W, Horstmann R, Doty P, et al. No influence of the new antiepileptic drug SPM 927 on th ECG time intervals QTc and PR. [poster] Epilepsia. 2004;45(Suppl 7):Poster 1.265.
44. Biton V, Rosenfeld WE, Whitesides J, et al. Intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures. Epilepsia. 2008;49:418-424.
45. Kropeit D, Schiltmeyer B, Cawello W, Hammes W, Horstmann R. Bioequivalence of short-time infusions compared to oral administration of lacosamide. Epilepsia. 2004;45(Suppl 7):123.
46. Thomas D, Nickel B, Cawello W, Hammes W, Horstmann R. Bio-equivalence of Short-time infusions compared to oral administration of lacosamide. Epilepsia. 2006;47(Suppl 4).
47. Krauss G, Ben Menachem E, Mamenskiene R, et al. Intravenous lacosamide as replacement for oral lacosamide in subjects with partial seizures: a multicenter, open-label, inpatient trail examining safety and tolerability of 10- and 15-minute infusion durations. Epilepsia. 2007;48 (Suppl 6):3.303.
48. Krämer G, Heinzl S. Lacosamid. Stuttgart: Ligatur; 2008.
49. Sheets PL, Heers C, Stoehr T, Cummins TR. Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2-(acetylamino)-N- benzyl-3-methoxypropanamide], lidocaine, and carbamazepine. J Pharmacol Exp Ther. 2008;326:89-99.
50. Berning S, Kellinghaus C. Intravenous lacosamide for treatment of status epilepticus. Epilepsia. 2009;50(Suppl 6):49.
51. Kellinghaus C, Berning S, Besselmann M. Intravenous lacosamide as successful treatment for nonconvulsive status epilepticus after failure of first-line therapy. Epilepsy Behav. 2009;14:429-431.