Neuropeptide receptors as potential antiepileptic drug targets : focus on the ghrelin axis

Abstract

Epilepsy is a very serious neurological disorder which is often underrepresented. Around 50 million individuals worldwide have active epilepsy with recurrent seizures and in spite of the medical advances over the years, 30% of these patients remain as drug resistant (Pati 2010). Even after several years of research, there is still a lack of good understanding on the pathophysiology of seizure disorders (Perucca 2011). Investigators in this field believe that there is a great need for novel antiepileptic drugs (AEDs) that act differently than the drugs available on the market. The majority of AEDs act by blocking sodium channels (phenytoin, carbamazepine) or by the augment of GABAergic transmission (phenobarbital, valproic acid). A newer generation of AEDs has expanded therapeutic options, however these are not superior to the older drugs (Hitiris 2006). Patients with mesial temporal lobe epilepsy (mTLE) are among the most pharmacoresistant to these medications (Pati 2010). In order to attempt the rectification of this dilemma, the neuropharmacologist needs to not only try and find AEDs with new mechanisms of action, but to also keep in mind what information is currently available on the pathophysiology of epilepsy. It is clear that during the complicated process of epileptogenesis, several different mechanisms are taking place, thus one should ideally identify new compounds that are capable of targeting different pathways simultaneously. The focus of epilepsy researchers is to identify compounds that are not only capable of attenuating seizures (anticonvulsant), but are also antiepileptogenic (can prevent epilepsy) or disease-modifying (halting its progression).