Anticonvulsant drug effects on spontaneous thalamocortical rhythms in vitro: Phenytoin, carbamazepine, and phenobarbital

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Zhang YF and Coulter DA (1996) Anticonvulsant drug effects on spontaneous thalamocortical rhythms in vitro: Phenytoin, carbamazepine, and phenobarbital. Epilepsy Res 23:1 55–70.

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Abstract: When perfused with a medium containing no added Mg2+, rodent thalamocortical brain slices generate spontaneous generalized thalamocortical discharges of several types. Two of these discharges, termed simple and complex thalamocortical burst complexes (sTBCs and cTBCs), are physiologically and pharmacologically similar to the spike-wave discharges of generalized absence epilepsy and to the discharges underlying generalized tonic-clonic seizures, respectively. In a further characterization of the pharmacology of generalized thalamocortical discharges recorded in rodent thalamocortical slices, the actions of anticonvulsants effective in control of partial and generalized tonic-clonic seizures, but not generalized absence seizures, were studied on these rhythms. The effects of phenytoin, carbamazepine, and phenobarbital were tested against sTBCs and cTBCs recorded in vitro in rodent thalamocortical slices. When applied in clinically relevant concentrations, phenytoin and carbamazepine were very effective in reducing or blocking cTBCs. These drugs were much less effective in controlling sTBCs. Phenobarbital was effective in controlling both sTBCs and cTBCs, but the level of block was greater for cTBCs. Therefore, it appears that sTBCs and cTBCs are quite distinct in their relative sensitivity to anticonvulsant drugs, and this differential sensitivity parallels the relative effectiveness of these drugs in controlling generalized absence and generalized tonic-clonic seizures.

Keywords: Generalized absence epilepsy; Seizure; Spike-wave discharge; Generalized tonic-clonic seizure; Thalamus; Cortex

Context

Using a specialized slice preparation that includes both thalamus and cortex, Zhang and Coulter lowered magnesium in the artificial cerebrospinal fluid bathing the tissue, presumably reducing block of the NMDA-type glutamate receptor, resulting in bursts of activity in thalamus and cortex. Classifying these bursts as simple or complex, the authors find that the three widely used anti-seizure drugs mentioned in the title greatly reduce complex bursts, but have less impact on simple bursts. Additional study of NMDAR in ictogenesis in Rafiq et al., 1995 from the same group.

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