Anticonvulsant drug effects on spontaneous thalamocortical rhythms in vitro: Ethosuximide, trimethadione, and dimethadione

被引:32
作者
Zhang, YF
Gibbs, JW
Coulter, DA
机构
[1] VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,DEPT NEUROL,RICHMOND,VA 23298
[2] VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,DEPT ANAT,RICHMOND,VA 23298
[3] VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,COMPREHENS EPILEPSY INST,RICHMOND,VA 23298
关键词
generalized absence epilepsy; seizure; spike-wave discharge; generalized tonic-clonic seizure; thalamus; cortex;
D O I
10.1016/0920-1211(95)00079-8
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Spontaneous generalized epileptiform discharges were elicited in rodent thalamocortical slices by perfusion with a medium containing no added Mg2+. In multiple-channel extracellular field potential recordings in thalamus and cortex, several distinct types of discharges were recorded, with two principal variants bearing marked similarity to spike-wave and generalized tonic-clonic seizure discharges recorded in patients with generalized seizure disorders, These discharges were termed sTBCs and cTBCs, respectively, for simple and complex thalamocortical burst complexes. The sensitivity of these discharges to the generalized absence anticonvulsants ethosuximide, trimethadione and dimethadione (the active metabolite of trimethadione) was studied. sTBCs were reduced or blocked by ethosuximide and dimethadione, when these drugs were applied in clinically relevant concentrations. The order of effectiveness of these agents was dimethadione greater than or equal to ethosuximide >> trimethadione. This paralleled the relative efficacy of these drugs in blocking T current in thalamic neurons. cTBCs were unaffected or exacerbated by these drugs. Structural control drugs including succinimide, the behaviorally inactive ring base of ethosuximide, and alpha,alpha-dimethyl-beta-methylsuccinimide, a convulsant succinimide, were inactive or exacerbated either sTBCs or cTBCs, respectively. These spontaneous generalized thalamocortical discharges in rodent thalamocortical slices may represent a potentially valuable in vitro model of generalized seizure discharges, with marked pharmacological and physiological similarities to various forms of clinical epileptic seizure activity.
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页码:15 / 36
页数:22
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