Neurochemical Research

, Volume 41, Issue 6, pp 1365–1374 | Cite as

Effect of the Anti-depressant Sertraline, the Novel Anti-seizure Drug Vinpocetine and Several Conventional Antiepileptic Drugs on the Epileptiform EEG Activity Induced by 4-Aminopyridine

  • Maria Sitges
  • Blanca Irene Aldana
  • Ronald Charles Reed
Original Paper
First Online:
Received:
Revised:
Accepted:

Abstract

Seizures are accompanied by an exacerbated activation of cerebral ion channels. 4-aminopyridine (4-AP) is a pro-convulsive agent which mechanism of action involves activation of Na+ and Ca2+ channels, and several antiepileptic drugs control seizures by reducing these channels permeability. The antidepressant, sertraline, and the anti-seizure drug vinpocetine are effective inhibitors of cerebral presynaptic Na+ channels. Here the effectiveness of these compounds to prevent the epileptiform EEG activity induced by 4-AP was compared with the effectiveness of seven conventional antiepileptic drugs. For this purpose, EEG recordings before and at three intervals within the next 30 min following 4-AP (2.5 mg/kg, i.p.) were taken in anesthetized animals; and the EEG-highest peak amplitude values (HPAV) calculated. In control animals, the marked increase in the EEG-HPAV observed near 20 min following 4-AP reached its maximum at 30 min. Results show that this epileptiform EEG activity induced by 4-AP is prevented by sertraline and vinpocetine at a dose of 2.5 mg/kg, and by carbamazepine, phenytoin, lamotrigine and oxcarbazepine at a higher dose (25 mg/kg). In contrast, topiramate (25 mg/kg), valproate (100 mg/kg) and levetiracetam (100 mg/kg) failed to prevent the epileptiform EEG activity induced by 4-AP. It is concluded that 4-AP is a useful tool to elicit the mechanism of action of anti-seizure drugs at clinical meaningful doses. The particular efficacy of sertraline and vinpocetine to prevent seizures induced by 4-AP is explained by their high effectiveness to reduce brain presynaptic Na+ and Ca2+ channels permeability.

Keywords

Carbamazepine Lamotrigine Levetiracetam Oxcarbazepine Phenytoin Topiramate Valproic acid 
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Notes

Acknowledgments

The authors thank Araceli Guarneros and Luz Maria Chiu for technical assistance. Funding for this study was provided in part by Programa de Apoyos para la Superación Académica de la UNAM (PASPA). All experiments were conducted in compliance with the ARRIVE guidelines.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Maria Sitges
    • 1
  • Blanca Irene Aldana
    • 2
  • Ronald Charles Reed
    • 3
  1. 1.Departamento de Biología Celular y Fisiología, Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoMexicoMexico
  2. 2.Department of Drug Design and Pharmacology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  3. 3.Department of Pharmacy PracticeHusson UniversityBangorUSA

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