Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: An isobolographic analysis

Fleck, Juliana; Marafiga, Joseane Righes; Jesse, Ana Cláudia; Ribeiro, Leandro Rodrigo; Rambo, Leonardo Magno; Mello, Carlos Fernando

doi:10.1016/j.phrs.2015.02.001

Cited by 11 publications

(11 citation statements)

References 52 publications

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“…These findings are in agreement with the current view that CysLT 1 inverse agonists decrease seizures ( 10 , 11 ), and extend from previous data showing that systemic montelukast impairs kindling induction with PTZ ( 9 ). It has recently been demonstrated that the CysLT 1 inverse agonist montelukast synergistically increases the anticonvulsant action of phenobarbital against PTZ-induced seizures.…”

Section: Discussionsupporting

confidence: 93%

“…In addition, kainic acid-induced seizures are associated with increased brain levels of leukotrienes and PGF 2α in the cortex, hippocampus and hypothalamus of rats ( 8 ). In accordance with these findings, a role for leukotriene receptors, particularly of the CysLT 1 subtype, has been proposed in seizure/epilepsy ( 8 9 10 11 ). Although LTD 4 (a CysLT 1 receptor agonist) facilitates pentylenetetrazol (PTZ)-induced seizures, intracerebroventricular ( icv ) injection of montelukast (a CysLT 1 receptor inverse agonist) decreases PTZ-induced seizures.…”

Section: Introductionmentioning

confidence: 58%

“…It has recently been demonstrated that the CysLT 1 inverse agonist montelukast synergistically increases the anticonvulsant action of phenobarbital against PTZ-induced seizures. Moreover, LTD 4 , a cysteinyl leukotriene, reverses the effect of montelukast ( 11 ). Indeed, epilepsy is associated with increased levels of inflammatory mediators in the brain, including leukotrienes, which are produced by neurons, glia, and endothelial cells in the BBB ( 16 , 17 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although LTD 4 (a CysLT 1 receptor agonist) facilitates pentylenetetrazol (PTZ)-induced seizures, intracerebroventricular ( icv ) injection of montelukast (a CysLT 1 receptor inverse agonist) decreases PTZ-induced seizures. In addition, icv montelukast prevents PTZ-induced blood-brain barrier (BBB) disruption and leukocyte infiltration ( 10 ), and potentiates the anticonvulsant effect of phenobarbital on PTZ seizures and decreases sedation, a major side effect of phenobarbital ( 11 ). Montelukast attenuates PTZ-induced myoclonic jerks and increases oxidative stress markers in rats ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

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Montelukast reduces seizures in pentylenetetrazol-kindled mice

Fleck

Temp

Marafiga

et al. 2016

Braz J Med Biol Res

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Montelukast reduces seizures in pentylenetetrazol-kindled mice

Fleck

Temp

Marafiga

et al. 2016

Braz J Med Biol Res

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“…The straight line (additive line) is made by dose A and dose B (EC 50 value). The EC 50 values (A and B) were transformed with 95% confidence (Fleck and others ). Dashed lines were the theoretically additive standard error.…”

Section: Introductionmentioning

confidence: 99%

The Evaluation of Antioxidant Interactions among 4 Common Vegetables using Isobolographic Analysis

Jiang

et al. 2015

Journal of Food Science

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Isobolographic analysis was used to assess the antioxidant interactions (synergism, addition, and antagonism) of 4 common vegetables (tomato [T], carrot [C], eggplant [E], and purple potato [P]). The lipophilic (L) extracts of T and C (main carotenoids), the hydrophilic (H) extracts of E and P (main phenolics) were mixed by the certain ratios (1:9, 3:7, 1:1, 7:3, 9:1, w/w) and their antioxidant activities were investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical scavenging assays, respectively. Most of the binary mixtures (LC-HE, LC-HP, HE-HP, LT-HE, and LT-HP combinations) showed the synergistic antioxidant effects. In DPPH assay, the greatest antioxidant activity of vegetable combinations was 1:9 LT-HP (EC50 : 2.45 ± 0.13 mg/mL), followed by 9:1 HE-HP (EC50 : 3.62 ± 0.12 mg/mL) and 1:9 LC-HE (EC50 : 3.74 ± 0.47 mg/mL). In ABTS assay, the greatest antioxidant activity of vegetable combinations was 9:1 HE-HP (EC50 : 4.20 ± 0.10 mg/mL), followed by 7:3 HE-HP (EC50 : 4.41 ± 0.63 mg/mL) and 1:1 HE-HP (EC50 : 5.35 ± 0.85 mg/mL). Among these combinations, 1:1 LC-HE combination showed the highest synergistic antioxidant effects in DPPH assay (synergistic rate: 87.4%), and 7:3 LC-HE combination showed the highest synergistic antioxidant effects in ABTS assay (synergistic rate: 87.0%). The mixtures of phenolics and carotenoids with suitable ratios in vegetables effectively enhanced the synergistic antioxidant effects.

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The role of human CYP2C8 in the metabolizing of montelukast-like compounds: a computational study

Ghadari

2017

Res Chem Intermed

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Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: An isobolographic analysis

Cited by 11 publications

References 52 publications

Montelukast reduces seizures in pentylenetetrazol-kindled mice

Montelukast reduces seizures in pentylenetetrazol-kindled mice

The Evaluation of Antioxidant Interactions among 4 Common Vegetables using Isobolographic Analysis

The role of human CYP2C8 in the metabolizing of montelukast-like compounds: a computational study

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