Drugs Under Clinical Trial

Perucca, Emilio

doi:10.1007/978-3-642-60072-2_21

Cited by 8 publications

(14 citation statements)

References 66 publications

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“…Levetiracetam, the S-enantiomer of alpha-ethyl-2-oxo-1-pyrrolidine acetamide which has been approved as monotherapy or as an adjunctive therapy for partial-onset seizures, has an incompletely characterized mechanism of action that includes inhibition of N-type calcium channels with possibly alterations in either GABAergic (10) or other neurotransmitter (e.g., glycine, benzodiazepine, adenosine, and various excitatory amino acid-related receptors)-related systems downstream (11).…”

Section: Discussionmentioning

confidence: 99%

Levetiracetam in Meige's syndrome

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Levetiracetam in Meige's syndrome

et al. 2006

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“…During subsequent chronic treatment, the anticonvulsant efficacy of LEV was markedly reduced, thus indicating development of tolerance (Figs. [2][3][4][5]. After 3 weeks of treatment, none of the seizure parameters were significantly altered by LEV.…”

Section: Anticonvulsant Efficacy Of Lev During Chronic Treatment In Fmentioning

confidence: 99%

“…A further remarkable feature of LEV in animal studies was its low neurotoxicity (2). In controlled clinical trials in patients with refractory partial epilepsy, a significant reduction in seizure frequency was obtained during add-on treatment with LEV (2). Remarkably, 8% of patients became seizure free under treatment with 3000 mg/d (2).…”

mentioning

confidence: 99%

Development of Tolerance During Chronic Treatment of Kindled Rats With the Novel Antiepileptic Drug Levetiracetam

2000

Epilepsia

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Purpose: Levetiracetam (LEV) is an interesting novel antiepileptic drug with proven efficacy in both animal models and patients with partial epilepsy. To study whether the efficacy of the drug changes during chronic treatment, we evaluated the anticonvulsant activity of LEV during prolonged daily administration in amygdala-kindled rats.Methods: On the basis of the anticonvulsant potency and duration of action after acute doses, LEV was administered in fully kindled rats three times daily at 108 mg/kg i.p. for 3 weeks. For the study of anticonvulsant efficacy, the afterdischarge threshold was determined before, during, and after the drug treatment period. To determine whether the pharmacokinetics of the drug change during prolonged treatment, LEV levels were repeatedly determined in plasma during the treatment period.Results: LEV markedly increased the afterdischarge thresh-old and decreased the seizure severity and duration after initial dosing, but a marked loss of anticonvulsant efficacy developed during chronic treatment. This loss of efficacy was not due to alterations in drug elimination, indicating the development of functional tolerance to LEV during repeated administration. After the termination of treatment, no withdrawal signs (e.g., changes in behavior, body temperature, body weight, or seizure threshold) were observed.Conclusions: The data demonstrate that chronic administration of LEV leads to a significant reduction in anticonvulsant efficacy in the kindling model of temporal lobe epilepsy. Whether this experimental observation has clinical relevance must await monotherapy trials with long-term follow-up of patients who initially responded to LEV.

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“…Levetiracetam (LEV; ucb L059), a pyrrolidone derivative, is an interesting novel antiepileptic drug (1,2). Preclinical results from studies in rodents have shown that the drug offers broad-spectrum seizure protective activity in a variety of animal models, including models for absence, generalized, and partial seizures (1,3).…”

mentioning

confidence: 99%

“…Furthermore, recent experiments in kindled rats indicate that in addition to its anticonvulsant activity, LEV may also possess antiepileptogenic activity (4). A further remarkable feature of LEV in animal studies was its low neurotoxicity (2). In controlled clinical trials in patients with refractory partial epilepsy, a significant reduction in seizure frequency was obtained during add-on treatment with LEV (2).…”

mentioning

confidence: 99%

Development of Tolerance During Chronic Treatment of Kindled Rats With the Novel Antiepileptic Drug Levetiracetam

2000

Epilepsia

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Drugs Under Clinical Trial

Cited by 8 publications

References 66 publications

Levetiracetam in Meige's syndrome

Levetiracetam in Meige's syndrome

Development of Tolerance During Chronic Treatment of Kindled Rats With the Novel Antiepileptic Drug Levetiracetam

Development of Tolerance During Chronic Treatment of Kindled Rats With the Novel Antiepileptic Drug Levetiracetam

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