selurampanel and Epilepsy

Epilepsy is a neurological disorder that significantly impacts the quality of life of affected persons. Despite advances in research, nearly a third of patients have refractory or pharmacoresistant epilepsy. Even though numerous antiepileptic drugs (AEDs) have been approved over the past decade, there are no agents that halt the development of epilepsy. Thus, new and improved AEDs to prevent these conditions are necessary.. We highlight recent advances in new and innovative drugs for epilepsy disorders. We review three small molecule drugs in phase II clinical trials: Cannabidivarin, BGG492 (Selurampanel) and Ganaloxone.. The full potential of Cannabidivarin will be realized by testing in other types of treatment-resistant seizures; if they are beneficial, larger phase III clinical trials would probably be undertaken in the same patient population. About BGG492, the challenge will be to find 'superselective' AMPAR antagonists targeting only calcium-permeable receptors, with specific mechanisms, that may be attractive partners for drugs in polytherapy. Moreover, there is anew interest surrounding Ganaloxone because of a new submicron formulation that improves its absorption and pharmacokinetic profile, but new studies are necessary before progressing. Further clinical innovations will define the future for these small molecule-type drugs in epilepsy therapeutics.

Topics: Animals; Anticonvulsants; Cannabinoids; Clinical Trials, Phase II as Topic; Drug Design; Drug Resistant Epilepsy; Drugs, Investigational; Epilepsy; Humans; Pregnanolone; Quality of Life; Quinazolinones

AMPA-type glutamate receptor (AMPAR) antagonism is under development as a novel mechanism of action for antiepileptic drugs. Selurampanel (BGG492) is an experimental competitive AMPA antagonist currently in clinical trials.. This article provides a review of the roles of glutamate receptors, especially of the AMPA type, in normal and epileptic synaptic transmission. It also provides a discussion of the mechanisms of action of AMPAR antagonist compounds. The article includes a summary of the preclinical and clinical data on the efficacy and safety of BGG492 and provides a discussion of the future role of these compounds in clinical therapy.. Since many persons with epilepsy remain inadequately treated, compounds exploiting new mechanisms for seizure control are welcome. Based on available clinical trial data as adjunctive therapy, the AMPAR antagonists will likely be highly useful in a small subset of persons and moderately helpful in a larger subset, similar to other new drugs for epilepsy developed since 1993. It remains impossible to predict which patients will respond to which class of drugs.

Topics: Animals; Anticonvulsants; Epilepsy; Humans; Quinazolinones; Receptors, AMPA; Receptors, Kainic Acid; Treatment Outcome