Modulation of leukotriene D4 attenuates the development of seizures in mice

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

“…Moreover, phenidone and BW755C, dual inhibitors of LOX/COX pathways, decrease kainic acid-induced seizures, suggesting the involvement of leukotrienes in this effect [10,11]. In line with this view, Rehni and Singh (2011) have shown that montelukast, a CysLT 1 receptor inverse agonist [12] and1,2,3,4-tetrahydroisoquinoline, regarded as a LTD 4 synthetic pathway inhibitor, dose-dependently suppress the development of kindled seizures, as well as pilocarpine-induced spontaneous recurrent seizures [13]. Similarly, Liu and colleagues (2014) have shown that zileuton, a 5-LOX inhibitor, decreases spike-wave discharges in pilocarpine epileptic rats [14].…”

“…Recent pharmacological evidence, however, suggests that non-prostanoid arachidonic acid-derived molecules, such as leukotrienes, produced via LOX, also play a role in seizures [13]. The early findings by Palmer and colleagues (1981) that LTD 4 increases neuronal firing rate together with the demonstration that montelukast and a putative synthetic LTD 4 pathway inhibitor dose-dependently suppress the development of kindled seizures, as well as pilocarpine-induced spontaneous recurrent seizures, support this view [16].…”

“…wakefulness) from basal and after treatment periods were identified in EEG recording and divided in 15 s segments and a 4 s epoch from each segment (without artifacts) was used to carry out the power analysis by the conversion into frequency domain by fast Fourier transformation (FFT) method. The resultant power values displayed for each frequency were grouped into 5 bands represented by delta (0.1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and gamma . For power analysis of decomposed waves, the power sum from all frequencies (0.1-80 Hz) was considered as 100%.…”

Cysteinyl Leukotrienes as Potential Pharmacological Targets for Cerebral Diseases

“…Nevertheless, only few studies have investigated the role for LOX-derived arachidonic acid metabolites in epilepsy [160–162]. Leukotriene levels were found to increase in a time-dependent manner in the brain during kainate-induced seizures in rats [160], and LTD4 i.c.v.…”

“…In line, montelukast and 1,2,3,4, tetrahydroisoquinoline, a LTD4 synthetic pathway inhibitor, suppressed the development of kindled seizures, as well as pilocarpine-induced spontaneous recurrent seizures in mice [162]. Bay-u9973, a nonselective CysLT receptor antagonist, montelukast, and pranlukast increased the latency to generalized seizures and decreased the mean amplitude of electroencephalogram (EEG) recordings during seizures in PTZ-injected mice [163].…”