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

摘要: Although leukotrienes have been implicated in seizures, no study has systematically investigated whether the blockade of CysLT1 receptors synergistically increases anticonvulsant action classic antiepileptics. In this study, behavioral and electroencephalographic methods, as well isobolographic analysis, are used to show that inverse agonist montelukast phenobarbital against pentylenetetrazole-induced seizures. Moreover, it is shown LTD4 reverses effect montelukast. The experimentally derived ED50mix value for a fixed-ratio combination (1:1 proportion) plus was 0.06±0.02 μmol, whereas additively calculated ED50add 0.49±0.03 μmol. interaction index 0.12, indicating synergistic interaction. association significantly decreased antiseizure ED50 (0.74 0.04 μmol absence presence montelukast, respectively) and, consequently, phenobarbital-induced sedation at equieffective doses. demonstration strong synergism between particularly relevant because both drugs already clinics, foreseeing an immediate translational application epileptic patients who drug-resistant