Review: Is levetiracetam different from other antiepileptic drugs? Levetiracetam and its cellular mechanism of action in epilepsy revisited

Abstract

Levetiracetam (LEV) is a new antiepileptic drug that is clinically effective in generalized and partial epilepsy syndromes as sole or add-on medication. Nevertheless, its underlying mechanism of action is poorly understood. It has a unique preclinical profile; unlike other antiepileptic drugs (AEDs), it modulates seizure-activity in animal models of chronic epilepsy with no effect in most animal models of acute seizures. Yet it is effective in acute in-vitro 'seizure' models. A possible explanation for these dichotomous findings is that LEV has different mechanisms of actions, whether given acutely or chronically and in 'epileptic' and control tissue. Here we review the general mechanism of action of AEDs, give an updated and critical overview about the experimental findings of LEV's cellular targets (in particular the synaptic vesicular protein SV2A) and ask whether LEV represents a new class of AED.

Conformational Preference and Spectroscopical Characteristics of the Active Pharmaceutical Ingredient Levetiracetam

“…It is worth mentioning here that for the gas-phase conformers, only the NH… O IMHBs are observed, if present. In this case, the (12), (13), and (17)- (22) conformers do not show any kind of IMHB.…”

“…Thus, the most important deviations are noted in case of F 2 dihedral for the conformer (4) and the F 1 as well as F 3 dihedrals for conformer (13). On the other hand, the conformational space of LEV in gas phase is quite distinct from those in water and ethanol solutions.…”

“…The 1 H and 13 C NMR spectra were recorded at room temperature on a Bruker AVANCE NMR spectrometer (400.13 MHz for 1 H and 100.63 MHz for 13 C, internal standard TMS). The samples were prepared by the dissolution of LEV in D 2 O (signal for 1 H at 4.78).…”

“…10 Its mechanism of action is distinct from that of the other antiepileptic drugs, [11][12][13][14] being presumed that it acts by modulating the function of the synaptic vesicle glycoprotein SV2A. [14][15][16][17][18][19][20][21][22] Its interesting pharmacokinetic properties together with its distinct chemical structure and mechanism of action make LEV unique among the marketed antiepileptic drugs.…”

The role of complement in epilepsy: a specific focus on C5ar1 and its role in seizure initiation and disease development

“…The anticonvulsant profile of PMX53 is similar to that of levetiracetam , which binds to the synaptic protein SV2a, but in addition is postulated to act via other mechanisms that are still undefined (Madeja et al, 2003, Surges et al, 2008. Lack of effect of PMX53 in the PTZ and MEST models suggest mechanisms of action independent from GABAA receptors and sodium channels.…”