Excitatory amino acid neurotransmission through both NMDA and non-NMDA receptors is involved in the anticonvulsant activity of felbamate in DBA/2 mice

Sarro, G. De; Ongini, Ennio; Bertorelli, Rosalia; Aguglia, Umberto; Sarro, Angela De

doi:10.1016/0014-2999(94)90022-1

Cited by 62 publications

(44 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, this effect can be detected at concentrations (300 gM) that are in the range of those achieved in the rat brain following the administration of anticonvulsant doses of felbamate (Adusumalli et al 1993). In addition, glycine and d-serine, a glycine site agonist, produce a rightward shift of the EDso for felbamate against audiogenic, electroshock-, NMDA-, and AMPA-induced seizures in mice (Coffin et al 1994;De Sarro et al 1994). It is noteworthy, however, that this hypothesis has been challenged by a recent study using radioligand binding assays and electrophysiological methods (Subramaniam et al 1995).…”

Section: Discussionmentioning

confidence: 80%

“…Thus, there is growing evidence that felbamate may have an inhibitory effect on NMDA receptor-mediated neurotransmission, although the molecular mechanisms involved have not yet been clearly defined (Coffin et al 1994;De Sarro et al 1994;Rho et al 1994;Subramaniam et al 1995;Taylor et al 1995). In addition, felbamate appears to have blocking effects on voltage-gated Na + channels and Ca 2+ conductances in the mammalian brain (White et al 1992;Libri and Constanti 1994).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, felbamate blocks the convulsions induced by NMDA and ~-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (De Sarro et al 1994), antagonizes tonic extension seizures elicited by maximal electroshock and, at higher doses, increases the threshold for PTZ-and picrotoxininduced seizures (Swinyard et al 1986). Although the mechanism of action of felbamate is not yet fully understood, it has been recently proposed that its ability to antagonize acute seizures may be due to an inhibition of NMDA receptor-mediated excitatory synaptic responses (McCabe et al 1993;Coffin et at.…”

Section: Introductionmentioning

confidence: 99%

“…Although the mechanism of action of felbamate is not yet fully understood, it has been recently proposed that its ability to antagonize acute seizures may be due to an inhibition of NMDA receptor-mediated excitatory synaptic responses (McCabe et al 1993;Coffin et at. 1994;De Sarro et al 1994;Subramaniam et al 1995) and a concomitant facilitation of GABAA receptor-mediated synaptic inhibition (Rho et al 1994;Subramaniam et al 1995). On the other hand, there is a relative paucity of data on the efficacy of felbamate in animal models of epilepsy using chronically recurring spontaneous or stimulus-induced seizures (Lockard et al 1987;De Sarro et al 1994).…”

Section: Introductionmentioning

confidence: 99%

“…1994;De Sarro et al 1994;Subramaniam et al 1995) and a concomitant facilitation of GABAA receptor-mediated synaptic inhibition (Rho et al 1994;Subramaniam et al 1995). On the other hand, there is a relative paucity of data on the efficacy of felbamate in animal models of epilepsy using chronically recurring spontaneous or stimulus-induced seizures (Lockard et al 1987;De Sarro et al 1994). Therefore, the present study was designed to examine the anticonvulsant action of felbamate in rats chronically treated with PTZ.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Anticonvulsant effect of felbamate in the pentylenetetrazole kindling model of epilepsy in the rat

Giorgi

Carboni

Frau

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

The present study was designed to examine the ability of felbamate, a novel antiepileptic agent, to antagonize the increase in seizure severity (i.e., chemical kindling) produced by chronic treatment with initially subconvulsant doses of pentylenetetrazol (PTZ). Rats were treated with PTZ (30 mg/kg, i.p., three times a week) for 8 consecutive weeks. Two other groups of rats received felbamate (300 or 400 mg/kg, i.p.), 90 min before each dose of PTZ. Pretreatment with felbamate at either dose prevented the progression of rank of seizures during chronic treatment with PTZ. Thus, the mean seizure score by the end of the chronic treatment (0-5 scale) was 0 in vehicle treated controls, 3.3 in rats treated with PTZ alone, 1.5 in rats treated with PTZ plus felbamate (300 mg/kg, i.p.) and 0.9 in the group treated with PTZ plus felbamate (400 mg/kg, i.p.). Felbamate also antagonized the long-term increase in the sensitivity to the convulsant effects of GABA function inhibitors observed in PTZ-kindled rats. Thus, the administration of a challenge dose of isoniazid (120 mg/kg, s.c.), picrotoxin (1.5 mg/kg, i.p.) or PTZ itself (15 mg/kg, i.p.), 15 to 45 days after the end of the chronic treatment regimen, induced convulsions in > 80% of PTZ-kindled rats and in < 20% of rats treated with PTZ + felbamate (400 mg/kg). The results are discussed in terms of the multiple mechanisms that can contribute to the anticonvulsant action of felbamate in the PTZ kindling model of epilepsy.

show abstract

Section: Discussionmentioning

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Anticonvulsant effect of felbamate in the pentylenetetrazole kindling model of epilepsy in the rat

Giorgi

Carboni

Frau

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

show abstract

Scientific Review and Clinical Applications

Levinson¹

2002

JAMA

View full text Add to dashboard Cite

IN THIS ISSUE OF THE JOURNAL, WE ARE BEGINNING A series entitled "Scientific Review and Clinical Applications." This series includes the review of a common clinical topic based on the most recent evidence, accompanied by an article applying the information to typical patients treated frequently in an office or hospital. Our goal is to provide readers with the best available information to guide clinical care and to answer questions that arise routinely in practice.Practicing physicians are challenged regularly by questions pertinent to the care of patients. Often the questions are not about rare conditions but common clinical problems. For example, what is the most recent evidence about the treatment for this condition? Are there recommended guidelines that should be followed? Of all the new diagnostic tests, which are the most appropriate for this condition and how much do they cost? In addition, many practical questions are not often addressed in scientific journal articles. For example, what tools can be used in the office setting to improve the care of patients with this condition? How should this complicated treatment decision be discussed with patients? Is there a Web site that can provide patients with accurate and clear information? The new series is designed to answer many of these common questions.The Scientific Review article is designed to present results of key randomized trials, meta-analyses, and highquality studies on the topic. This review includes a description of how the key articles were selected for inclusion in the review. Tables summarize the studies so readers can refer to the original scientific work as needed. The authors point out the gaps in information and consider the possible approaches that physicians can use when clear evidence is unavailable.The Clinical Applications article applies the scientific information from the review to specific patient cases. Some of the cases fit the available evidence well, and others are designed to illustrate situations in which patients and physicians need to make decisions despite the lack of clear evidence. The cost of different diagnostic tests and therapies is presented when possible or practical. In addition, the authors provide resources for patient education so physicians can refer patients to high-quality Web sites. Tools to facilitate office practice are provided when available.In this issue we present the first 2 articles in this series, a comprehensive, systematic review of oral hypoglycemic agents for type 2 diabetes mellitus by Inzucchi 1 and a thoughtful discussion of the practical application of this information by Holmboe 2 that illustrates the therapeutic options for primary care physicians treating patients with type 2 diabetes. The Scientific Review and Clinical Applications series will be a regular feature in the Clinician's Corner. 3 We welcome ideas for submissions and invite potential authors to contact Wendy Levinson, MD, at wendy.levinson @utoronto.ca. We also welcome your feedback so we can improve the series to make it mos...

show abstract