[Neuronal and neurochemical mechanisms underlying the effect of a novel antiepileptic drug levetiracetam].
Published data on the mechanisms involved in the action of levetiracetam (LVT, 2S-(oxo-1-pyrrolidinyl)butanoic acid amide), a widely used agent for the adjunctive therapy of partial epilepsy of different genesis, have been analyzed. A unique profile of the anticonvulsant action of LVT was already revealed at the screening stage: this agent was not effective in the traditional tests, but it demonstrated a pronounced protective effect in kindling models and in the experiments on mice sensitive to the audiogenic convulsions. Now it is commonly accepted that the LVT mode of action is different from that of the other known antiepileptic drugs. LVT was shown to have specific binding sites in the brain. It is believed that the synaptic vesicle protein SV2A is the binding site for LVT, and the main mechanism of its action involves the modulation of this protein functions, which probably accounts for the unique profile of the antiepileptic activity of LVT. The results of investigations of the neurochemical mechanisms of LVT action suggest that proteins involved in the vesicular exocytosis, in particular SV2, can be promising targets in the search for new effective agents for the treatment of CNS diseases.
Raevskiĭ
K S
KS
Malikova
L A
LA
Kalinin
V V
VV
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004828:Epilepsies, Partial / Q000188:drug therapy*; D004829:Epilepsy, Generalized / Q000188:drug therapy*; D005089:Exocytosis; D006801:Humans; D000077287:Levetiracetam; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*
D000927:Anticonvulsants; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C489614:Sv2a protein, mouse; D000077287:Levetiracetam; D010889:Piracetam