The effects of a novel GluK2 receptor antagonist UBP2002 on epileptogenesis (360G-Wellcome-207209_Z_17_Z)

Glutamate is the major excitatory transmitter in the mammalian CNS and is involved in key physiological functions and in a variety of neurological conditions, including stroke, chronic pain, anxiety and epilepsy. The actions of glutamate are mediated via four classes of receptors: AMPA, Kainate, NMDA and Metabotropic. Kainate receptors (KARs) are composed of five subunits (GluK1-5). KARs are involved in many physiological functions, however they have also been implicated in the pathophysiology of epilepsy. Little is known about the physiological roles of KARs in neurological disorders, compared with the other glutamate receptor classes, mainly due to the lack of selective drugs. Recently this setting started to change with the development of selective GluK1 antagonists. This project aims to test the ability of a novel GluK2 antagonist UBP2002 (produced at the University of Bristol) to prevent the development of and to reverse epileptic activity induced by electrical stimulation on Hippocampal slices. Current antiepileptic drugs (AEDs), although effective in controlling epileptic seizures in the majority of patients, have limited efficacy against drug resistant epilepsies. Therefore, there is a need for new drugs acting on different targets than those of currently available AEDs and for the development of new therapies for epilepsy.