Levetiracetam: The profile of a novel anticonvulsant drug - Part I: Preclinical data

被引:57
作者
De Smedt, Tim [1 ]
Raedt, Robrecht [1 ]
Vonck, Kristl [1 ]
Boon, Paul [1 ]
机构
[1] Ghent Univ Hosp, Dept Neurol, Lab Clin & Expt Neurophysiol, Reference Ctr Refractory Epilepsy, B-9000 Ghent, Belgium
来源
CNS DRUG REVIEWS | 2007年 / 13卷 / 01期
关键词
anticonvulsants; epilepsy; levetiracetam; SV2A;
D O I
10.1111/j.1527-3458.2007.00004.x
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
The objective of this article was to review and summarize the available reports on the preclinical profile of the novel anticonvulsant drug levetiracetam (LEV). Therefore, a careful search was conducted in the MEDLINE database and combined with guidelines from regulatory agencies, proceedings of professional scientific meetings, and information provided by the manufacturers. This article provides detailed information on the anticonvulsant effects of LEV in various animal models of epilepsy and on its pharmacology in laboratory animals. The mechanism of action of LEV is reviewed, with special regard to its recently discovered binding site, the synaptic vesicle protein 2A. In general, LEV is shown to be a safe, broad-spectrum anticonvulsant drug with highly beneficial pharmacokinetic properties and a distinct mechanism of action. The clinical studies with LEV will be discussed in the second part of this review article to be published subsequently.
引用
收藏
页码:43 / 56
页数:14
相关论文
共 87 条
[1]
Levetiracetam reduces caffeine-induced Ca2+ transients and epileptiform potentials in hippocampal neurons [J].
Ängehagen, M ;
Margineanu, DG ;
Ben-Menachem, E ;
Rönnbäck, L ;
Hansson, E ;
Klitgaard, H .
NEUROREPORT, 2003, 14 (03) :471-475
[2]
Comparative pharmacokinetics and metabolism of levetiracetam, a new anti-epileptic agent, in mouse, rat, rabbit and dog [J].
Benedetti, MS ;
Coupez, R ;
Whomsley, R ;
Nicolas, JM ;
Collart, P ;
Baltes, E .
XENOBIOTICA, 2004, 34 (03) :281-300
[3]
Levetiracetam (ucb L059) affects in vitro models of epilepsy in CA3 pyramidal neurons without altering normal synaptic transmission [J].
Birnstiel, S ;
Wulfert, E ;
Beck, SG .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1997, 356 (05) :611-618
[4]
Antiepileptic drugs and apoptotic neurodegeneration in the developing brain [J].
Bittigau, P ;
Sifringer, M ;
Genz, K ;
Reith, E ;
Pospischil, D ;
Govindarajalu, S ;
Dzietko, M ;
Pesditschek, S ;
Mai, I ;
Dikranian, K ;
Olney, JW ;
Ikonomidou, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (23) :15089-15094
[5]
Effects of levetiracetam on spike and wave discharges in WAG/Rij rats [J].
Bouwman, BM ;
van Rijn, CM .
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY, 2004, 13 (08) :591-594
[6]
The antiepileptic drug levetiracetam decreases the inositol 1,4,5-trisphosphate-dependent [Ca2+]i increase induced by ATP and bradykinin in PC12 cells [J].
Cataldi, M ;
Lariccia, V ;
Secondo, A ;
di Renzo, G ;
Annunziato, L .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 313 (02) :720-730
[7]
Multiple mechanisms underlying the neuroprotective effects of antiepileptic drugs against in vitro ischemia [J].
Costa, C ;
Martella, G ;
Picconi, B ;
Prosperetti, C ;
Pisani, A ;
Di Filippo, M ;
Pisani, F ;
Bernardi, G ;
Calabresi, P .
STROKE, 2006, 37 (05) :1319-1326
[8]
Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A) [J].
Crowder, KM ;
Gunther, JM ;
Jones, TA ;
Hale, BD ;
Zhang, HZ ;
Peterson, MR ;
Scheller, RH ;
Chavkin, C ;
Bajjalieh, SM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :15268-15273
[9]
Synaptic vesicle protein 2 enhances release probability at quiescent synapses [J].
Custer, KL ;
Austin, NS ;
Sullivan, JM ;
Bajjalieh, SM .
JOURNAL OF NEUROSCIENCE, 2006, 26 (04) :1303-1313
[10]
De Deyn P., 1992, NEUROSCIENCES-JPN, V18, P187