This paper comprises a series of experiments in rodent models of partial and
generalized epilepsy which were designed to describe the anti-
convulsant profile of the functionalized
amino acid lacosamide.
Lacosamide was effective against sound-induced
seizures in the genetically susceptible Frings mouse, against maximal electroshock test (MES)-induced
seizures in rats and mice, in the rat hippocampal kindling model of
partial seizures, and in the 6Hz model of psychomotor
seizures in mice. The activity in the MES test in both mice (4.5mg/kg i.p.) and rats (3.9 mg/kg p.o.) fell within the ranges previously reported for most clinically available anti-epileptic drugs. At both the median effective dose for MES protection, as well as the median toxic dose for rotorod impairment,
lacosamide elevated the seizure threshold in the i.v.
pentylenetetrazol seizure test, suggesting that it is unlikely to be pro-
convulsant at high doses.
Lacosamide was inactive against
clonic seizures induced by subcutaneous administration of the chemoconvulsants
pentylenetetrazol,
bicuculline, and
picrotoxin, but it did inhibit
NMDA-induced
seizures in mice and showed full efficacy in the
homocysteine model of
epilepsy. In summary, the overall anti-
convulsant profile of
lacosamide appeared to be unique, and the
drug displayed a good margin of safety in those tests in which it was effective. These results suggest that
lacosamide may have the potential to be clinically useful for at least the treatment of generalized tonic-clonic and partial-onset
epilepsies, and support ongoing clinical trials in these indications.