Evidence for a differential interaction of brivaracetam and levetiracetam with the synaptic vesicle 2A protein

• DOI: 10.1111/epi.13638
• Publication Date: 2016-12-25T05:26:17Z
• Authors: Martyn D. Wood; Michel Gillard
• Keywords: Radioligand; Levetiracetam

Brivaracetam (BRV) and levetiracetam (LEV) are effective antiepileptic drugs that bind selectively to the synaptic vesicle 2A (SV2A) protein. However, BRV differs from LEV in it exhibits more potent complete seizure suppression animal models including amygdala-kindled mice, where afforded nearly suppression. This raises possibility aside potency differences, may interact differently with SV2A protein, which is not apparent radioligand-binding competition studies. In this study, we used a recently identified allosteric modulator, UCB1244283, appears induce conformational changes SV2A, probe binding properties of labeled LEV.Radioligand studies were carried out using [3 H]BRV H]LEV. Studies performed membranes both recombinant cells expressing human protein brain tissue.The modulator increased radioligands but by different mechanisms. For H]BRV, increase was driven mainly an affinity, whereas for H]LEV, due number sites. Kinetic confirmed differential effect.These suggest act at sites or states It possible some pharmacologic differences between could be interactions