A novel anti-epileptic agent, perampanel, selectively inhibits AMPA receptor-mediated synaptic transmission in the hippocampus

作者：Ceolin Laura; Bortolotto Zuner A; Bannister Neil; Collingridge Graham L; Lodge David; Volianskis Arturas^*

来源：Neurochemistry International, 2012, 61(4): 517-522.

DOI：10.1016/j.neuint.2012.02.035

• Perampanel
• GYKI52466
• D-AP5
• AMPA receptors
• NMDA receptors
• Kainate receptors

Perampanel is a non-competitive AMPA receptor antagonist that is under development as an anti-epileptic therapy. Although it is known to reduce calcium flux mediated by AMPA receptors in cultured cortical neurons, there are no studies of its selectivity in synaptic transmission in more intact systems. In the present study using hippocampal slices, perampanel (0.01-10 mu M) has been tested on pharmacologically isolated synaptic responses mediated by AMPA, NMDA or kainate receptors. Perampanel reduced AMPA receptor-mediated excitatory postsynaptic field potentials (f-EPSPs) with an IC50 of 0.23 mu M and a full block at 3 mu M. This compares with an IC50 of 7.8 mu M for GYKI52466 on these responses. By contrast, perampanel at 10 mu M had no effect on responses mediated by NMDA or kainate receptors, which were completely blocked by 30 mu M D-AP5 and 10 mu M NBQX respectively. The concentrations of perampanel required to reduce AMPA receptor-mediated responses are not dissimilar to those in plasma following anti-convulsant doses and are consistent with AMPA receptor antagonism being its primary mode of action.

• 出版日期2012-9