title: Montelukast reduces seizures in pentylenetetrazol-kindled mice.
abstract: Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Montelukast (10 mg/kg, sc) and phenobarbital (20 mg/kg, sc) increased the latency to generalized seizures in kindled mice. Montelukast increased CysLT1 immunoreactivity only in non-kindled, PTZ-challenged mice. Interestingly, PTZ challenge decreased CysLT2 immunoreactivity only in kindled mice. CysLT1 antagonists appear to emerge as a promising adjunctive treatment for refractory seizures. Nevertheless, additional studies are necessary to evaluate the clinical implications of this research.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.
authors.forename: J
authors.initials: J
authors.lastname: Fleck
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.
authors.forename: F R
authors.initials: FR
authors.lastname: Temp
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.
authors.forename: J R
authors.initials: JR
authors.lastname: Marafiga
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.
authors.forename: A C
authors.initials: AC
authors.lastname: Jesse
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.
authors.forename: L H
authors.initials: LH
authors.lastname: Milanesi
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.
authors.forename: L M
authors.initials: LM
authors.lastname: Rambo
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil.
authors.forename: C F
authors.initials: CF
authors.lastname: Mello
mesh_terms: D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D003292:Convulsants; D003521:Cyclopropanes; D007696:Kindling, Neurologic / Q000187:drug effects; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D010634:Phenobarbital / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D018077:Receptors, Leukotriene / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013440:Sulfides; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D000927:Anticonvulsants; D003292:Convulsants; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; C083169:leukotriene D4 receptor; C093875:montelukast; D010433:Pentylenetetrazole; D010634:Phenobarbital