Targeting α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors in epilepsy

Citraro, Rita; Aiello, Rossana; Franco, Valentina; Sarro, Giovambattista De; Russo, Emilio

doi:10.1517/14728222.2014.874416

Cited by 42 publications

(31 citation statements)

References 131 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is a hetero-oligomer formed from GluA1, GluA2, GluA3 andGluA4 subunits (Citraro et al, 2014). AMPA receptor-mediated transmission may contribute to the enhancement of cortical excitability and, as a consequence, to SWD generation.…”

Section: Ampa Receptorsmentioning

confidence: 99%

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Russo

Citraro

Constanti³

et al. 2016

Neuroscience & Biobehavioral Reviews

Self Cite

128

View full text Add to dashboard Cite

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development.Neuroscience and Biobehavioral Reviews http://dx.doi.org/10. 1016/j.neubiorev.2016.09.017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe WAG/Rij rat model has recently gathered attention as a suitable animal model of absence epileptogenesis. This latter term has a broad definition encompassing any possible cause that determines the development of spontaneous seizures; however, most of, if not all, preclinical knowledge on epileptogenesis is confined to the study of post-brain insult models such as traumatic brain injury or post-status epilepticus models. WAG/Rij rats, but also synapsin 2 knockout, Kv7 current-deficient mice represent the first examples of genetic models where an efficacious antiepileptogenic treatment (ethosuximide) was started before seizure onset. In this review, we have critically reconsidered all articles published regarding WAG/Rij rats, from the perspective that the period before SWD onset is considered as the latent period. In our new theory on seizure development, it is proposed that genes might be considered as the initial "insult" responsible for all plastic changes underpinning the development of spontaneous seizures. According to this idea, in WAG/Rij rats, genetic predisposition would lead to the development of abnormal bilateral cortical epileptic foci, which would then nongenetically stimulate the rest of the brain to rearrange networks in order to phenotypically develop seizures similarly to what happens during electrical kindling.

show abstract

Section: Ampa Receptorsmentioning

confidence: 99%

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Russo

Citraro

Constanti³

et al. 2016

Neuroscience & Biobehavioral Reviews

Self Cite

128

View full text Add to dashboard Cite

show abstract

“…In particular, the availability of AEDs able to increase SE response after the failure of first‐line treatment and before the need of anesthetizing agents would be of paramount importance. By now, among the potential drugs and targets currently studied, those regulating excitatory transmission, blocking glutamate receptors of the AMPA subtype, have had relatively little consideration even though AMPA receptors (AMPARs) have been recognized to have a key role in ictogenesis and epileptogenesis . Competitive and noncompetitive AMPAR antagonists have antiseizure and antiepileptogenic effects in a broad range of in vitro and in vivo preclinical models .…”

Section: Status Epilepticus: Target Of Current Treatmentsmentioning

confidence: 99%

The role of AMPA receptors and their antagonists in status epilepticus

et al. 2018

Self Cite

View full text Add to dashboard Cite

Status epilepticus (SE) is typically defined as a prolonged self-sustaining seizure or repeated seizures showing an incomplete recovery between them. SE represents a medical emergency often associated with significant disability, morbidity, and mortality. Despite the clinical impact, the mechanisms underlying the transition from self-limited seizures to protracted, medically refractory seizures are not completely understood. About 40% of patients in established SE are refractory to antiepileptic drugs (first-line treatment); therefore, there is a need for more efficacious drugs. In this review, we focused on the current knowledge about the involvement of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors during SE, the preclinical efficacy of its antagonists, and the currently published clinical studies involving drugs with this mechanism of action. We carried out an extensive literature search to recognize experimental and clinical articles both on AMPA receptors and AMPA antagonists and SE. Recently, the role of AMPA receptors during and after SE has become clearer, and it is now widely accepted that early changes occur in the initial stages and probably contribute both to the maintenance of SE and to its refractoriness to treatment. The therapeutic potential of AMPA receptor inhibition has been sustained by studies in which AMPA receptor antagonists have been shown to terminate seizures in several SE animal models. To date, promising, but limited, data in humans support the use of AMPA receptor antagonists in patients with SE. AMPA receptor antagonists could become a new therapeutic option in patients with established SE when the first trials with second-line agents have failed or probably even better after failure of benzodiazepines as a second-line option.

show abstract

“…They are localized at excitatory synapses, post-synaptically. AMPA is the main receptor mediating rapid effects of glutamate and underlies the fast component of excitatory post-synaptic potential (EPSP) [6]. AMPA receptor exists in two states, closed, inactive state and open, active state.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Current role of perampanel in pediatric epilepsy

et al. 2017

Self Cite

View full text Add to dashboard Cite

Perampanel is among the latest AEDs approved, indicated for the treatment of partial-onset seizures with or without secondary generalization, and for primary generalized tonic-clonic seizures, in patients aged 12 years and older. This paper summarizes the clinical recommendations on the current role of perampanel in the treatment of pediatric epilepsies and future directions for research. The optimal dosage should be comprised between 4 and 12 mg/day, with 8 mg/day being the most common dosage used. The rate and severity of adverse events, including psychiatric symptoms, can be decreased by starting at low doses, and titrating slowly. Overall, perampanel presents an acceptable risk/benefit ratio, but special caution should be made to the risk of seizure aggravation and behavioral problems. The favorable cognitive profile, the ease of use of the titration scheme and the once-daily formulation offer advantage over other AEDs and make this drug particularly suitable for adolescent population. Perampanel is a welcome addition to the armamentarium of the existing AEDs, as it represents a new approach in the management of epilepsy, with a novel mechanism of action and a potential to have a considerable impact on the treatment of adolescents with epilepsy.

show abstract

Targeting α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors in epilepsy

Cited by 42 publications

References 131 publications

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

The role of AMPA receptors and their antagonists in status epilepticus

Current role of perampanel in pediatric epilepsy

Contact Info

Product

Resources

About