An in vitro investigation of the action of lamotrigine on neuronal voltage-activated sodium channels.
Lamotrigine (LTG), 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine, is a novel antiepieptic drug structurally unrelated to the major anticonvulsants in current use. Previous studies of LTG in rodents revealed efficacy in maximal electroshock test, pentylenetetrazol test and kindling models of seizures suggesting potential utility in the treatment of partial and generalized (tonic-clonic) seizures. In the present study, LTG was found to block sustained repetitive firing of sodium-dependent action potentials in mouse spinal cord cultured neurons and inhibit [3H]batrachotoxinin A 20-alpha-benzoate binding in rat brain synaptosomes suggesting a direct interaction with voltage-activated sodium channels.
Cheung
H
H
Department of Biology, Fisons Pharmaceuticals, Rochester, NY 14623.
Kamp
D
D
Harris
E
E
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002478:Cells, Cultured; D000077213:Lamotrigine; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology*
D000927:Anticonvulsants; D015222:Sodium Channels; D014227:Triazines; D000077213:Lamotrigine