Anticonvulsant effects of levetiracetam and levetiracetam-diazepam combinations in experimental status epilepticus.
Status epilepticus (SE) is a neurological emergency, with high mortality and high morbidity among survivors, and novel therapeutic agents are needed to improve this picture. We examined the effects of the antiepileptic drug levetiracetam (LEV) in an experimental model of self-sustaining status epilepticus (SSSE), induced in rats by electrical stimulation of the perforant path. LEV's unique spectrum of anticonvulsant activity, very high therapeutic index, and neuroprotective properties, make it a potentially interesting agent in the treatment of SE. Pretreatment with LEV intravenously reduced (30 mg/kg) or prevented (50-1000 mg/kg) the development of self-sustaining seizures. Treatment during the maintenance phase of SSSE diminished (at 200 mg/kg) or aborted seizures (in doses of 500 or 1000 mg/kg). Addition of LEV significantly enhanced the anticonvulsant effects of diazepam (DZP), even when both drugs where given in doses far below their therapeutic level. We conclude that LEV deserves further evaluation in the treatment of status epilepticus.
Mazarati
Andrey M
AM
Department of Neurology, Geffen School of Medicine at UCLA, Los Angeles, CA, USA. mazarati@ucla.edu
Baldwin
Roger
R
Klitgaard
Henrik
H
Matagne
Alain
A
Wasterlain
Claude G
CG
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004558:Electric Stimulation / Q000379:methods; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D013226:Status Epilepticus / Q000188:drug therapy* / Q000503:physiopathology
D000927:Anticonvulsants; D000077287:Levetiracetam; D003975:Diazepam; D010889:Piracetam