Inhibition of calcium-permeable and calcium-impermeable AMPA receptors by perampanel in rat brain neurons
- Neurosci Lett. 2016 Oct 28;633:146-151. doi: 10.1016/j.neulet.2016.09.028.
- 1. I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, 194223, Torez pr. 44, Saint-Petersburg, Russia. Electronic address: [email protected].
Perampanel is an antiepileptic drug that is used to treat partial-onset seizures and generalized tonic-clonic seizures. It is a highly selective AMPA Receptor allosteric antagonist. However, published data on perampanel activity vary in different studies. In the present work we studied the inhibition of native calcium-permeable and calcium-impermeable AMPA receptors in rat brain neurons by perampanel using whole-cell patch clamp technique. We found that inhibitory activity and kinetics of perampanel action do not differ between calcium-permeable AMPA receptors of rat giant striatum interneurons and calcium-impermeable receptors of hippocampal CA1 pyramidal neurons (the IC50 value about 60nM). Also, perampanel caused the same inhibition of steady-state currents induced by kainate and glutamate. From the other side perampanel-induced inhibition was markedly reduced in the presence of cyclothiazide (IC50 value increased to 1.2±0.2μM). We demonstrated that perampanel competes with GYKI-52466 for binding site.