Short communicationAge-related decrease in the antiseizure effect of ifenprodil against pentylenetetrazole in mice
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Acknowledgements
This work was supported in part by a Grant-in-Aid from The Tokyo Biochemical Research Foundation and a Research Grant from the Ministry of Health and Welfare to T. Suzuki. We wish to thank Ms. Sachiko Komiya and Ms. Miho Soma for their expert technical assistance.
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Sigma-1 receptor and seizures
2023, Pharmacological ResearchEpileptiform GluN2B–driven excitation in hippocampus as a therapeutic target against temporal lobe epilepsy
2022, Experimental NeurologyCitation Excerpt :Ictogenic processes are one of the prime targets in medication aiming at suppression of seizure initiation (Blauwblomme et al., 2014; Lillis and Staley, 2018). While the role of NMDARGluN2B in the pathophysiology of seizure initiation has been well examined in models of acute convulsions (De Sarro et al., 1997, 1995; Doyle and Shaw, 1996; Pontecorvo et al., 1991; Tsuda et al., 1997), it has not been sufficiently studied in recurrent seizures in TLE. Ifenprodil, a selective antagonist of NMDARGluN2B, has been demonstrated to decrease neuronal excitability in lateral temporal lobe and neocortex resections from epileptic patients with cortical dysplasia (Möddel et al., 2005; Wang et al., 2017).
Does status epilepticus modify the effect of ifenprodil on cortical epileptic afterdischarges in immature rats?
2018, Pharmacological ReportsCitation Excerpt :The same age-dependent effects were demonstrated with another NR2B antagonist Ro 25-6981 [20]. All our data are in agreement with results in mice, where ifenprodil injected either intraperitoneally or intracerebroventricularly exhibited anticonvulsant action against pentetrazol-induced seizures only during the first two postnatal weeks [21]. Interpretation of our data is complicated by effects of lithiuim-paraldehyde treatment.
The NMDA receptor complex as a therapeutic target in epilepsy: A review
2011, Epilepsy and BehaviorCitation Excerpt :Ifenprodil (4-[2-(4-benzylpiperidin-1-yl)-1-hydroxypropyl]phenol) selectively blocks the polyamine site at the NR2B subunit of the NMDAR. Several preclinical studies have shown that ifenprodil exerts anticonvulsant effects in a variety of animal models of epilepsy including seizures induced by NMDA, spermine, lindane, and PTZ in rodents [336–340]; spinal seizures in mice induced by handling following pretreatment with a sub-convulsive dose of strychnine [341]; the MES test [230,336,342]; audiogenic seizures in genetically epilepsy-prone rats [151,343]; motor and electrocortical seizures induced by unilateral local injection of putrescine into the rat deep prepiriform cortex [326]; ethanol withdrawal seizures in mice [344]; amygdala-kindling development [345]; proconvulsive effects of interleukin(IL)-1β on electrographic seizures induced by intrahippocampal injection of kainic acid in C57BL6 adult mice [346]; PTZ-induced seizures in spermidine/spermine N1-acetyltransferase transgenic mice [347]; cocaine-induced convulsions and lethality in mice [237]; prolonged status epilepticus induced by continuous hippocampal stimulation [348]; and activity evoked by intracortical stimulation in brain slices from freeze-lesioned rat neocortex [349]. However, it is noteworthy that ifenprodil had no effect in some animal models.
NMDA NR2B subtype-selective receptor antagonists fail to antagonize electrically-precipitated seizures and elicit popping in mice
2010, European NeuropsychopharmacologyDifferent effects of two N-methyl-d-aspartate receptor antagonists on seizures, spontaneous behavior, and motor performance in immature rats
2009, Epilepsy and BehaviorCitation Excerpt :The anticonvulsant activity of ifenprodil is markedly different from that of memantine: ifenprodil was able to specifically suppress the tonic phase of generalized tonic–clonic seizures in 7-, 12-, and 18-day-old rats, but not in the oldest group studied. This developmental change is in agreement with the results of Tsuda et al. in mice [25], who reported an anticonvulsant effect of ifenprodil in 7- and 10-day-old mice but not in older mice. The difference in age when the change took place might be due to a difference in the doses used (only the 20-mg/kg dose in Tsuda and colleagues’ study) and to the lower sensitivity of mice and faster metabolism in this smaller rodent species.