Levetiracetam in Experimental Status Epilepticus.
Abstract number :
1.276
Submission category :
Year :
2001
Submission ID :
1697
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
C.G. Wasterlain, MD, VA Medical Center (127), Los Angeles, CA; A.M. Mazarati, MD, PhD, Neurology, VAMC, Los Angeles, CA; H.V. Klitgaard, PhD, Preclinical CNS Research, UCB SA Pharma Sector, Braine-l[ssquote]Alleud, Belgium; R.A. Baldwin, MS, Neurology, VM
RATIONALE: Levetiracetam (LEV) is an effective antiepileptic agent with neuroprotective properties (Hanon and Klitgaard, Seizure, in press). Its antikindling efficacy makes it a potentially interesting compound for the treatment of self-sustaining status epilepticus (SSSE), a condition which is maintained by plastic changes in excitatory neurotransmission. Here we report its efficacy in an animal model of status epilepticus.
METHODS: We used a rat model of SSSE induced by perforant path stimulation (PPS) for 30 minutes in awake animals. LEV or diazepam was injected iv 10 minutes before or 10 minutes after the end of PPS. Seizures and spikes were recorded continuously and detected by Harmonie software.
RESULTS: LEV showed a dose-dependent reduction of SSSE. When injected before PPS, LEV (50 mg/kg) reduced total seizure time from 606 to 7 minutes, and higher doses reduced it further. Post-PPS treatment required higher doses. LEV 200 mg/kg cut total seizure time to 322 minutes, LEV 500 mg/kg reduced it to 22 minutes and 1000 mg/kg to 10 minutes (p[lt]0.05).
CONCLUSIONS: LEV is highly effective in the treatment of experimental SSSE, and high dose treatment is more effective than diazepam (5-10 mg/kg) in this model.
Support: The Research Service of VHA, Grant NS 13515 from NINDS, and a grant from UCB Pharma.
Disclosure: Salary - Klitgaard -UCB Pharma; Grant - Wasterlain - UCB Pharma