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Montelukast reduces seizures in pentylenetetrazol-kindled mice

J Fleck1, F R Temp1, J R Marafiga1

  • 1Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.

Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas
|February 25, 2016
PubMed

Insights

Montelukast, a cysteinyl leukotriene receptor 1 antagonist, reduced seizure frequency in PTZ-kindled mice. This suggests CysLT1 antagonists may offer a novel adjunctive therapy for refractory epilepsy.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Epilepsy Research

Background:

  • Cysteinyl leukotrienes (CysLTs) are implicated in seizure activity.
  • The role of CysLT receptor antagonists in kindled seizures and their impact on receptor expression remains unexplored.

Purpose of the Study:

  • To investigate the efficacy of montelukast (CysLT1 inverse agonist) and phenobarbital in reducing seizures in pentylenetetrazol (PTZ)-kindled mice.
  • To examine changes in CysLT receptor expression following PTZ-induced kindling.

Main Methods:

  • PTZ-kindled mice were treated with montelukast or phenobarbital.
  • Seizure latency was measured.
  • CysLT1 and CysLT2 receptor immunoreactivity was assessed in brain tissue.

Main Results:

  • Both montelukast and phenobarbital significantly increased the latency to generalized seizures in kindled mice.
  • Montelukast elevated CysLT1 immunoreactivity in non-kindled, PTZ-challenged mice.
  • PTZ challenge decreased CysLT2 immunoreactivity specifically in kindled mice.

Conclusions:

  • CysLT1 receptor antagonists show potential as adjunctive treatments for refractory seizures.
  • Further research is required to determine the clinical applicability of these findings.

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