The novel antiepileptic drug levetiracetam (ucb L059) appears to act via a specific binding site in CNS membranes

European Journal of Pharmacology
M NoyerE Wülfert

Abstract

Levetiracetam ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide, ucb L059) is a novel potential antiepileptic agent presently in clinical development with unknown mechanism of action. The finding that its anticonvulsant activity is highly stereoselective (Gower et al., 1992) led us to investigate the presence of specific binding sites for [3H]levetiracetam in rat central nervous system (CNS). Binding assays, performed on crude membranes, revealed the existence of a reversible, saturable and stereoselective specific binding site. Results obtained in hippocampal membranes suggest that [3H]levetiracetam labels a single class of binding sites (nH = 0.92 +/- 0.06) with modest affinity (Kd = 780 +/- 115 nM) and with a high binding capacity (Bmax = 9.1 +/- 1.2 pmol/mg protein). Similar Kd and Bmax values were obtained in other brain regions (cortex, cerebellum and striatum). ucb L060, the (R) enantiomer of levetiracetam, displayed about 1000 times less affinity for these sites. The binding of [3H]levetiracetam is confined to the synaptic plasma membranes in the central nervous system since no specific binding was observed in a range of peripheral tissues including heart, kidneys, spleen, pancreas, adrenals, lungs and liver. The commonly us...Continue Reading

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