Differential Effects of Antiepileptic Drugs and Beta-Carbolines on Seizures Induced by Excitatory Amino Acids

Neuroscience. 1990;39(3):799-807. doi: 10.1016/0306-4522(90)90262-3.

Abstract

Agonists acting at subtypes of glutamate receptors, N-methyl-D-aspartate, kainate and quisqualate, induce convulsions in rodents. Clonic seizures induced in mice by intracerebral administration of N-methyl-D-aspartate, kainate or quisqualate were used to study the anti- and proconvulsant potential of antiepileptic drugs and beta-carbolines. Systemic administration showed that the benzodiazepines clonazepam and midazolam blocked convulsions induced by kainate and had no effect on seizures triggered by N-methyl-D-aspartate and quisqualate. In contrast, diazepam blocked convulsions induced by either excitatory amino acid, as did valproate. The benzodiazepine receptor agonist beta-carboline ZK 93423 blocked convulsions induced by kainate but had no effect on seizures induced by N-methyl-D-aspartate or quisqualate. The antagonist beta-carboline ZK 93426 did not affect convulsions induced by excitatory amino acids, while the inverse agonists FG 7142 and ethyl-beta-carboline-3-carboxylate increased the sensitivity of mice to kainate. Phenobarbital and 2-chloroadenosine protected mice against seizures induced by quisqualate and kainate, while baclofen was active against convulsions produced by kainate. MK-801 selectively blocked convulsions induced by N-methyl-D-aspartate, and enhanced the susceptibility of mice to seizures triggered by kainate and quisqualate. Ethosuximide increased the susceptibility of mice to N-methyl-D-aspartate and had little or no effect on other types of seizures. Diphenylhydantoin enhanced the convulsant potential of quisqualate. Trimethadione and carbamazepine did not affect convulsions induced by N-methyl-D-aspartate, kainate or quisqualate. Intracerebral administration of midazolam protected mice against seizures induced by kainate. Ethosuximide increased the susceptibility of mice to N-methyl-D-aspartate, while diphenylhydantoin to quisqualate convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Carbolines / pharmacology*
  • Convulsants*
  • Kainic Acid / toxicity*
  • Male
  • Mice
  • Mice, Inbred Strains
  • N-Methylaspartate / toxicity*
  • Quisqualic Acid / toxicity*
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Seizures / physiopathology

Substances

  • Anticonvulsants
  • Carbolines
  • Convulsants
  • N-Methylaspartate
  • Quisqualic Acid
  • Kainic Acid