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Related Experiment Video

Updated: Apr 26, 2026

Behavioral Characterization of Pentylenetetrazole-induced Seizures: Moving Beyond the Racine Scale
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Cysteinyl leukotriene receptor (CysLT) antagonists decrease pentylenetetrazol-induced seizures and blood-brain

Q F Lenz1, D S Arroyo2, F R Temp1

  • 1Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil; Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.

Neuroscience
|August 6, 2014
PubMed
Summary
This summary is machine-generated.

Montelukast and other CysLT receptor antagonists reduce seizures and preserve blood-brain barrier integrity. These findings suggest cysteinyl leukotriene receptor 1 (CysLT1) antagonists are promising for developing new anticonvulsant therapies.

Keywords:
CysLT1Rleukotrienesmontelukastpentylenetetrazolseizure

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Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Inflammation is implicated in seizure pathophysiology, with pro-inflammatory arachidonic acid derivatives potentially facilitating seizures.
  • Leukotriene formation accompanies kainate-induced seizures and is reduced by LOX/COX pathway inhibitors.
  • Cysteinyl leukotriene receptor 1 (CysLT1) receptor antagonists, including montelukast, have shown promise in suppressing certain seizure models, but their effect on blood-brain barrier (BBB) integrity during seizures remains unexplored.

Purpose of the Study:

  • To investigate the anticonvulsant effects of montelukast and other CysLT receptor antagonists on pentylenetetrazol (PTZ)-induced seizures.
  • To determine if these antagonists preserve BBB integrity during PTZ-induced seizures.
  • To explore the role of LTD4 in modulating the anticonvulsant and BBB-protective effects of these antagonists.

Main Methods:

  • Adult male albino Swiss mice were used, with stereotaxic cannulation into the lateral ventricle and EEG recording electrodes placed over the parietal cortex.
  • Antagonists (montelukast, pranlukast, Bay u-9773) and/or LTD4 were administered intracerebroventricularly (i.c.v.) before PTZ administration.
  • Seizure activity was monitored electrographically and behaviorally, while BBB permeability was assessed using sodium fluorescein and confocal microscopy for CD45 and IgG immunoreactivity.

Main Results:

  • Montelukast, pranlukast, and Bay u-9773 significantly increased seizure latency and decreased seizure amplitude.
  • Montelukast demonstrated a dose-dependent protection against PTZ-induced BBB disruption, which was partially reversed by LTD4.
  • Confocal microscopy confirmed PTZ-induced BBB leakage and leukocyte infiltration, effects attenuated by montelukast and potentiated by LTD4.

Conclusions:

  • CysLT1 receptor antagonists, including montelukast, exhibit anticonvulsant properties against PTZ-induced seizures.
  • Montelukast's anticonvulsant effect may be partly mediated by its ability to maintain BBB integrity.
  • These findings highlight CysLT1 receptors as a potential therapeutic target for anticonvulsant drug development.