Effects of GYKI 52466 and some 2,3-benzodiazepine derivatives on hippocampal in vitro basal neuronal excitability and 4-aminopyridine epileptic activity

Eur J Pharmacol. 2000 Mar 10;391(1-2):75-80. doi: 10.1016/s0014-2999(00)00050-9.

Abstract

In order to determine whether the anticonvulsant effect of 2, 3-benzodiazepines is also displayed in a model of in vitro epilepsy, such as the "epileptiform" hippocampal slice, we studied the effects of 2,3-benzodiazepine 1-(4-aminophenyl)-4-methyl-7, 8-methylenedioxe-5H 2,3-benzodiazepine hydrochloride (GYKI 52466) and some new 2,3-benzodiazepine derivatives on CA1 basal neuronal excitability and on CA1 epileptiform burst activity produced by 4-aminopyridine in rat hippocampal slices. The results showed that GYKI 52466 affected basal neuronal excitability as evidenced by its influence on the magnitude of the CA1 orthodromic-evoked field potentials. 2,3-Benzodiazepines showed their antiepileptic effect also in an in vitro model of experimental epilepsy. The effects of the new 2,3-benzodiazepine derivatives suggest that the methylenedioxidation in positions 7 and 8 of the 2,3-benzodiazepine ring is the main structural modification for the antiepileptic effect of 2,3-benzodiazepines to take place.

MeSH terms

  • 4-Aminopyridine / antagonists & inhibitors*
  • 4-Aminopyridine / pharmacology
  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Anticonvulsants / pharmacology*
  • Axons / drug effects
  • Benzodiazepines / pharmacology*
  • Calcium Channel Blockers / pharmacology
  • Convulsants / antagonists & inhibitors*
  • Convulsants / pharmacology
  • Electrophysiology
  • Epilepsy / chemically induced
  • Epilepsy / physiopathology
  • Epilepsy / prevention & control*
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / physiopathology
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Neurons / drug effects*
  • Neurons, Afferent / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, Presynaptic / drug effects
  • Verapamil / pharmacology

Substances

  • Anti-Anxiety Agents
  • Anticonvulsants
  • Calcium Channel Blockers
  • Convulsants
  • Receptors, Presynaptic
  • GYKI 52466
  • Benzodiazepines
  • 4-Aminopyridine
  • Verapamil