Effects of Retigabine on the Neurodegeneration and Extracellular Glutamate Changes Induced by 4-Aminopyridine in Rat Hippocampus In Vivo

Mora, Gabriela De la Mora-De la; Tapia, Ricardo

doi:10.1007/s11064-005-8834-8

Cited by 17 publications

(8 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, Rekling (2003) found that RTG/ EZG did not protect hippocampal slice cultures against oxygen/glucose deprivation, although several other AEDs tested in their model were effective. In an in vivo model of neurodegeneration induced by hippocampal administration of 4AP, RTG/EZG reduced cell loss from the cornu ammonis-1 region measured 24 h post-4-AP (Mora & Tapia, 2005). Both drugs were infused via a dialysis probe, which allowed simultaneous measurement of extracellular glutamate.…”

Section: Neuroprotectionmentioning

confidence: 99%

The spectrum of anticonvulsant efficacy of retigabine (ezogabine) in animal models: Implications for clinical use

et al. 2012

View full text Add to dashboard Cite

SUMMARYRetigabine [RTG (international nonproprietary name); ezogabine (EZG; U.S. adopted name)] is a first-in-class antiepileptic drug (AED) that reduces neuronal excitability by enhancing the activity of KCNQ (K v 7) potassium (K + ) channels. RTG/EZG has recently been approved by the European Medicines Agency and the U.S. Food and Drug Administration as adjunctive therapy in adults with partial-onset seizures. In this review we discuss the activity that RTG/EZG has demonstrated across a broad spectrum of in vitro/in vivo animal models of seizures, including generalized tonic-clonic, primary generalized (absence), and partial seizures, in addition to the compound's ability to resist and block the occurrence of seizures induced by a range of stimuli across different regions of the brain. The potency of RTG/EZG in models refractory to several conventional AEDs and the work done to assess antiepileptogenesis and neuroprotection are discussed. Studies that have evaluated the central nervous system side effects of RTG/EZG in animals are reviewed in order to compare these effects with adverse events observed in patients with epilepsy. Based on its demonstrated effect in a number of animal epilepsy models, the synergistic and additive activity of RTG/EZG with other AEDs supports its potential use in therapeutic combinations for different seizure types. The distinct mechanism of action of RTG/EZG from those of currently available AEDs, along with its broad preclinical activity, underscores the key role of KCNQ (K v 7) K + channels in neuronal excitability, and further supports the potential efficacy of this unique molecule in the treatment of epilepsy.

show abstract

Section: Neuroprotectionmentioning

confidence: 99%

The spectrum of anticonvulsant efficacy of retigabine (ezogabine) in animal models: Implications for clinical use

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Although the drug might be effective in other seizure types, the study only evaluated its effects on partial-onset seizures. The investigators found that retigabine reduced seizures in this refractory group at a rate similar to other new antiepileptic drugs (12). The data indicate that 900 mg probably will be the median dose for this drug, as it produced fewer adverse effects than the 1200-mg dose (17% for the 600 mg arm, 20.2% for the 900 mg arm, and 29.2% for the 1200 mg arm).…”

Section: Commentarymentioning

confidence: 82%

Retigabine: Has the Orphan Found a Home?

Ben‐Menachem¹

2007

Epilepsy Curr

View full text Add to dashboard Cite

OBJECTIVE: To investigate the relationship between the apolipoprotein (ApoE) 4 allele and memory performance (verbal and nonverbal) in patients with medically intractable temporal lobe epilepsy (TLE) who underwent temporal lobectomy.METHODS: Presurgical and postsurgical memory performance was examined in 87 adult patients with TLE (4 = 22; non-4 = 65) to determine whether the expression of ApoE-4 may be associated with memory performance in this population and to examine how this relationship may be affected by duration of epilepsy. RESULTS: There was a significant interaction between ApoE-4 status and duration of epilepsy such that 4 carriers with a long duration of epilepsy demonstrated the poorest memory performance on both verbal and nonverbal measures. This relationship was observed both before and after temporal lobectomy, with little change in test performance over time. CONCLUSIONS: The ApoE-4 allele interacts with longstanding seizures to affect memory performance, both verbal and nonverbal, in patients with medically intractable temporal lobe epilepsy.

show abstract

“…Retigabine is one of the most recent drugs belonging to antiepileptics and it has a unique mechanism of action associated mainly with the activation of voltage-gated potassium channels Kv7 [1]. The drug also increases GABAergic transmission, primarily through GABA A receptors [2], inhibits glutamatergic transmission [3], and if administered at high doses, it blocks voltage-gated sodium and calcium channels [4]. Results of recent research indicate that retigabine may also inhibit striatal cholinergic interneuron activity [5].…”

Section: Introductionmentioning

confidence: 99%

Beneficial effect of retigabine on memory in rats receiving ethanol

2020

View full text Add to dashboard Cite

Background Retigabine belongs to the novel generation of antiepileptic drugs but its complex mechanism of action causes that the drug might be effective in other diseases, for instance, alcohol dependence. It is known that ethanol abuse impaired the function of brain structures associated with memory and learning such as the hippocampus. In our previous study, retigabine reduced hippocampal changes induced by ethanol in the EEG rhythms in rabbits. This study is focused on the impact of retigabine on memory processes in male rats receiving alcohol. Methods Memory was evaluated in various experimental models: Morris water maze, Contextual, and Cued Fear Conditioning tests. Retigabine was administered for 3 weeks directly to the stomach via oral gavage at a dose of 10 mg/kg. Rats received also 20% ethanol (5 g/kg/day in two doses) via oral gavage for 3 weeks and had free access to 5% ethanol in the afternoon and at night. Morris water maze was performed after 1 and 3 weeks of ethanol administration and after 1 week from the discontinuation of ethanol administration. Contextual and Cued Fear Conditioning tests were carried out after 24 h and 72 h of alcohol discontinuation. Results The drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration. Conclusions This beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug’s impact on the development of addiction.

show abstract

Effects of Retigabine on the Neurodegeneration and Extracellular Glutamate Changes Induced by 4-Aminopyridine in Rat Hippocampus In Vivo

Cited by 17 publications

References 52 publications

The spectrum of anticonvulsant efficacy of retigabine (ezogabine) in animal models: Implications for clinical use

The spectrum of anticonvulsant efficacy of retigabine (ezogabine) in animal models: Implications for clinical use

Retigabine: Has the Orphan Found a Home?

Beneficial effect of retigabine on memory in rats receiving ethanol

Contact Info

Product

Resources

About