Advances in neurology
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A variety of the anticonvulsant drugs, including carbamazepine, phenytoin, primidone, phenobarbital, clonazepam, valproic acid, and ethosuximide, are available for use in the treatment of patients with seizure disorders. These anticonvulsants vary in their efficacy against experimental seizures in animals and against seizures in humans. The mechanistic basis for this variability in anticonvulsant drug action remains uncertain, but numerous mechanisms of action have been proposed. ⋯ Based on these results, we have proposed that blockade of SRF may underlie the action of phenytoin, carbamazepine, phenobarbital, valproic acid, and benzodiazepines against generalized tonic-clonic seizures in humans and maximal electroshock seizures in animals. Enhancement of GABAergic synaptic transmission may underlie efficacy of benzodiazepines and valproic-acid drugs against generalized absence seizures in humans and pentylenetetrazol-induced seizures in experimental animals. The mechanism of action of ethosuximide against generalized absence seizures in humans and pentylenetetrazol-induced seizures in experimental animals may be by a third, as yet unknown, mechanism.
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Advances in neurology · Jan 1986
ReviewBenzodiazepine/barbiturate/GABA receptor-chloride ionophore complex in a genetic model for generalized epilepsy.
The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) acts through postsynaptic receptor sites which regulate membrane chloride ion channels. The GABA receptor-ionophore complex also contains modulatory receptor sites for two classes of centrally acting drugs, one for the benzodiazepines, and a second for both barbiturates and related depressants and for picrotoxin and related convulsants. The presence of these drug modulatory sites, directly on the GABA receptor protein, is consistent with other experimental observations; blocking GABA function can cause seizures, and augmenting GABA function can afford protection against seizures. ⋯ A 30% deficit in BZ receptor binding was observed in the midbrain of seizure-sensitive animals relative to normal controls. This was shown by quantitative brain-slice binding autoradiography to involve a decrease in the number of binding sites in the substantia nigra (SN) and periaqueductal gray regions. A deficit in membrane receptors for BZs (which are linked to a subtype of postsynaptic GABA receptors) in a crucial region of brain might therefore contribute to seizure susceptibility in some kinds of epilepsy.