Effects of antiepileptic drugs on thalamocortical excitability

Englander, Raymond N.; Johnson, Richard F.; Brickley, James J.; Hanna, George R.

doi:10.1212/wnl.27.12.1134

Cited by 22 publications

(6 citation statements)

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“…Considerable evidence concerning the neurosystems and cellular mechanisms of action of ESM suggests that this anticonvulsant exerts its effect through a facilitatory action on certain inhibitory systems rather than by causing a general membrane depression (Englander et al, 1977;Nowack et al, 1979;Barnes and Dichter, 1984). ESM has been demonstrated to attenuate thalamocortical activity in the frequency range cortically evoked by the convulsant PTZ (Englander et al, 1977;Gloor, 1968). The observed enhancement of metabolic activity in the mammillary circuit during ESM-induced attenuation of PTZ seizures may represent a unique neurosystem effect of ESM that is important in its anticonvulsant action against generalized PTZ convulsions.…”

Section: Discussionmentioning

confidence: 99%

Selective Metabolic Activation of the Mammillary Bodies and Their Connections During Ethosuximide‐Induced Suppression of Pentylenetetrazol Seizures

Mirski

Ferrendelli

1986

Epilepsia

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Electroencephalographic (EEG) activity and regional [14C]2-deoxyglucose incorporation in brain were examined in guinea pigs treated with pentylenetetrazol (PTZ), ethosuximide (ESM), phenytoin (PHT), or combinations of these drugs. Convulsant doses of PTZ induced EEG epileptiform discharges in paralyzed and ventilated animals and resulted in a large increase in labeled glucose accumulation in essentially all brain areas. ESM alone depressed EEG activity and accumulation of label, whereas PHT alone had little or no effect. Autoradiographs of PTZ-infused animals pretreated with PHT, which facilitated the onset and increased the severity of the PTZ seizures, were similar to those of animals treated with convulsant alone, with additional label uptake in the globus pallidus and substantia nigra. Pretreatment of PTZ-infused animals with sufficient ESM to prevent most EEG spike activity reduced glucose incorporation in most brain regions, but increased it in some. Selective enhancement of label uptake was observed in the mammillary bodies, mammillothalamic tracts, the anterior nuclei of the thalamus, the mammillary peduncles, and the dorsal and ventral tegmental nuclei of the midbrain. These data suggest that the mammillary nuclei and their projections to the anterior thalamic nucleus and their reciprocal projections to and from the tegmental nuclei may be important in the mediation of seizure activity induced by PTZ and/or the anticonvulsant action of ESM.

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Section: Discussionmentioning

confidence: 99%

Selective Metabolic Activation of the Mammillary Bodies and Their Connections During Ethosuximide‐Induced Suppression of Pentylenetetrazol Seizures

Mirski

Ferrendelli

1986

Epilepsia

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“…One might argue that in the rabbit experiments the dose used (30 mg/kg) was too high and far exceeded the recommended therapeutic dose. The latter however, was slightly lower than the 40mg/kg recommended by others [18] to achieve therapeutic level in cats.…”

Section: Discussionmentioning

confidence: 57%

The effect of diphenylhydantoin on the electroretinogram

et al. 1989

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Acute administration of diphenylhydantoin (DPH) in rabbits produces a significant increase in the amplitude of the a-wave. A marked increase in the amplitude of the b-wave is also noted but the time course is slower than that for the a-wave. While in controls the oscillatory potential (OP) recordings essentially consist of three major types, recordings taken after DPH injection consist of one major OP (OP2), which appears to be a result of the fusion of the original OP2 with another OP produced by the DPH injection. A similar blend of OPs was also seen in ERGs recorded from three human subjects on DPH therapy.

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“…The paradoxical facilitation of SI by CBZ and PHT is thus probably due to the combination of a depressant effect of these drugs on the tonic inhibition of S1, plus their depressant effect on excitatory transmission, outweighing their depressant effect on the S1 itself, Carbamazepine and PHT depress high-frequency firing of neurons in cell cultures but ESM does not (Macdonald, 1983;Barnes and Dichter, 1984;Macdonald et al, 1985). On the other hand, ESM does reduce repetitive firing in a number of synaptic systems in vivo (Capek and Esplin 1977;Englander et al, 1977, Nowack et al, 1979. These findings suggest that a common denominator of antiepileptic drug action is its ability to selectively inhibit paroxysmal firing in CNS neurons, enabling them to prevent seizures without significantly affecting normal rates of neuron activity.…”

Section: Discussionmentioning

confidence: 99%

Effect of Zonisamide (CI‐912) on a Synaptic System Model

1987

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The effect of the experimental antiepileptic drug zonisamide (1,2-benzisoxazole-3-methanesulfonamide, ZNS) on the trigeminal complex of cats was compared with the effect of established antiepileptic drugs. Intravenous administration of 10-40 mg/kg ZNS significantly depresses descending excitatory mechanisms, as well as segmental and descending inhibitory mechanisms, but has only a minor effect on segmental excitatory mechanisms. This spectrum of activity is similar to that of valproate, and suggests that ZNS should also be a broad-spectrum antiepileptic drug. In agreement with our experimental observations, it has been found that ZNS is effective against complex partial, generalized tonic clonic, and myoclonic seizures. The antiepileptic profile of ZNS in conventional screening tests resembles that of carbamazepine (CBZ) and phenytoin. However, CBZ exacerbates rather than prevents myoclonic seizures. Our experimental model thus provides a more accurate prediction of ZNS's clinical spectrum of activity. The relationship of these findings to the mechanism of action of antiepileptic drugs is discussed.

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Effects of antiepileptic drugs on thalamocortical excitability

Cited by 22 publications

References 0 publications

Selective Metabolic Activation of the Mammillary Bodies and Their Connections During Ethosuximide‐Induced Suppression of Pentylenetetrazol Seizures

Selective Metabolic Activation of the Mammillary Bodies and Their Connections During Ethosuximide‐Induced Suppression of Pentylenetetrazol Seizures

The effect of diphenylhydantoin on the electroretinogram

Effect of Zonisamide (CI‐912) on a Synaptic System Model

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