In vitro electrophysiological evidence predicting anticonvulsant efficacy of memantine and flunarizine.
Electrophysiological assays on mammalian central neurons in monolayer dissociated cell culture allow classification of clinically used anticonvulsant drugs on a mechanistic basis and predict their clinical spectrum of anticonvulsant efficacy consistently in comparison with data from animal models. Clinical anticonvulsant efficacy of memantine and flunarizine against tonic-donic and partial seizures is predicted on the basis of ability to limit sustained high efficacy frequency repetitive firing of sodium-dependent action potentials and to suppress depolarizing burst firing of neocortical, hippocampal and spinal cord neurons in cell culture. Effects on voltage-sensitive sodium channels, and possibly potassium channels, may explain, at least in part, the mechanism of anticonvulsant efficacy of memantine and flunarizine.
McLean
M J
MJ
Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37212.
D000547:Amantadine / Q000031:analogs & derivatives*; D000826:Animal Testing Alternatives; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005444:Flunarizine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy*
D000547:Amantadine; D005444:Flunarizine; D008559:Memantine