title: The anti-epileptic drug lacosamide (Vimpat) has anxiolytic property in rodents.
abstract: Lacosamide ((R)-2-acetamido-N-benzyl-3-methoxypropionamide; formerly harkoseride, SPM 927; Vimpat), has been recently approved by US and European regulatory authorities for use as add-on therapy for partial-onset seizures in adults. Because a number of anti-epileptic drugs are used to treat conditions beyond epilepsy, including anxiety, in the present study we investigated the anxiolytic potential of lacosamide in a conditioned emotional response (CER) model in rat, and the mouse marble burying assay. In each test lacosamide produced a significant effect consistent with anxiolysis, i.e. lacosamide increased suppression ratio in the CER test, and reduced the number of marbles buried in the marble burying assay. The doses necessary for an anxiolytic effect were higher than those necessary for efficacy in seizure tests conducted in the same species. For example in the mouse, the lacosamide oral ED(50) in the maximal electroshock seizure (MES) and 6 Hz tests was 5.3 and 9.6 mg/kg respectively, and the minimal effective dose in the marble burying assay was 30 mg/kg. In both seizure and anxiety tests, the (S)-enantiomer of lacosamide was inactive suggesting a similar mechanism of action, possibly use-dependent inhibition of sodium channel function (Errington et al., 2008). Efficacy in the CER model was equivalent to diazepam and pregabalin (Lyrica). In tests of side-effects, lacosamide had no effect on choice accuracy in the delayed match to position task of working memory, although at the 30 mg/kg dose, response rates and response latencies were significantly affected. In sum, the present results identify for the first time, an anxiolytic potential of lacosamide.
authors.affiliation: NPS Pharmaceuticals, 101 College Street, Toronto, ON M5G 0A3, Canada. guyh@cancog.com
authors.forename: Guy A
authors.initials: GA
authors.lastname: Higgins
authors.forename: Nathalie
authors.initials: N
authors.lastname: Breysse
authors.forename: Elijus
authors.initials: E
authors.lastname: Undzys
authors.forename: Calvin
authors.initials: C
authors.lastname: Kuo
authors.forename: Narges
authors.initials: N
authors.lastname: Joharchi
authors.forename: D Richard
authors.initials: DR
authors.lastname: Derksen
authors.forename: Tao
authors.initials: T
authors.lastname: Xin
authors.forename: Methvin
authors.initials: M
authors.lastname: Isaac
authors.forename: Malik
authors.initials: M
authors.lastname: Slassi
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D000078334:Lacosamide; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism
chemical_list: D000081:Acetamides; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D015222:Sodium Channels; D000078334:Lacosamide