LEVETIRACETAM INCREASES GLYCINE LEVELS IN PONS/MEDULLA OBLONGATA AFTER CHRONIC TREATMENT OF WISTAR RATS
Abstract number :
1.085
Submission category :
Year :
2004
Submission ID :
980
Source :
www.aesnet.org
Presentation date :
12/2/2004 12:00:00 AM
Published date :
Dec 1, 2004, 06:00 AM
Authors :
1Lasse Ormel, 2Bjornar Hassel, 1Leif Gjerstad, and 1Erik Tauboll
The new antiepileptic drug levetiracetam is effective against various types of epileptic attacks including myoclonic seizures (1,2). Its mechanism of action is still not known. However, levetiracetam may influence glycinergic transmission (3). The aim of the present study was to investigate the effect of levetiracetam and two other commonly used antiepileptic drugs on amino acid levels in different brain regions. Female Wistar rats were fed twice daily for 90 days through a gastric tube with either levetiracetam 50 mg/kg (n=6), 150 mg/kg (n=7), valproate 300 mg/kg (n=7), phenytoin 75 mg/kg (n=7) or control solution (n=7). We looked for changes in the levels of amino acids in frontal cortex, parietal cortex, hippocampus, cerebellum and pons/medulla oblongata. Levetiracetam (50 and 150 mg/kg) produced a significant increase in the tissue level of glycine in pons/medulla oblongata, but not in the other structures. In contrast, valproate and phenytoin decreased glycine levels compared to the control group in pons/medulla oblongata. Levetiracetam increased glycine levels in pons/medulla oblongata after chronic treatment. The increase in glycine levels by levetiracetam may contribute to augmentation of glycinergic neurotransmission in the brain stem, a structure believed to be important for the generation and control of myoclonus. This finding may help to explain the effect of levetiracetam on myoclonic seizures.
1: Kasteleijn-Nolst Trenite et al. (1996) Epilepsy Res 25, 225-230.
2. Agarwal and Frucht (2003) Curr Opin Neurol 16, 515-521.
3. Rigo et al (2002) Br J Pharmacol 136, 659-672.