Mode Of Action
The following video demonstrates the pharmacology of AMPA antagonism at AMPA receptors in the central nervous system. Glutamate is the main excitatory neurotransmitter in the brain, which is involved in the propagation of an action potential from the pre-synaptic neuron to the post-synaptic neuron. Excessive glutamate release has been observed during seizure activity in humans, contributing to the pathophysiology of epilepsy.
FYCOMPA — THE FIRST AND ONLY LICENSED AMPA RECEPTOR ANTAGONIST
Reduce postsynaptic hyperexcitation
Fycompa is a highly selective, noncompetitive, AMPA receptor antagonist 1,2 Fycompa reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity
at postsynaptic AMPA receptors 1,2,4
A HIGHLY SELECTIVE, NONCOMPETITIVE AMPA RECEPTOR ANTAGONIST
Selective 4
Selectively binds to AMPA receptors No significant affinity for NMDA or kainate receptors*
*At therapeutic levels there was no impact on NMDA or kainate.4
Noncompetitive AMPA receptor antagonist 3
Binds to the AMPA receptor at a noncompetitive site Does not directly block glutamate from binding
Inhibits activation of the AMPA receptor
References: 1. Fycompa Summary of Product Characteristics, July 2012 Eisai Europe Limited. 2. Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Curr. 2011(2);11;56-63. 3. Hanada T, Hashizume Y, Tokuhara N, et al. Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia. 2011;52(7):1331-1340. 4. Ceolin L, Bortolotto Z, Bannister N, et al. A novel anti-epileptic agent, perampanel, selectively inhibits AMPA receptor-mediated synaptic transmission in the hippocampus. Neurochem Int. 2012. http://dx.doi.org/10.1016/j.neuint.2012.02.035.