Abstract: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 Fragment-based drug discovery for allosteric sites, PPI’s... and the future . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 Targeting protein−protein interactions using small-molecule fragments and an antibody platform . . . . . . . . . . . . . . . . . . . . . . 149 Antibodies as tools in NCE discovery . . . . . . . . . . . . . . . . . . . . . . . 150 Challenges and opportunities in allosteric enzyme inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Phenotypic screening approaches for the discovery of novel antimalarials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 Bicycles: high affinity bicyclic peptides from phage display libraries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Leading into new spaces – strategies for lead generation in neuroscience medicinal chemistry . . . . . . . . . . . . . . . . . . . . . . . . 154 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

Abstract: SUMMARY Effective treatment of epilepsy has been the main therapeutic challenge for the past several years. The biggest problem is refractory epilepsy. Despite the fact that the problem of seizure resistance to monotherapy affects approximately 30% of epileptic patients, clear algorithms of drug selection have not been yet fully developed. Considering the treatment with two or more antiepileptic drugs (AEDs), it is of particular importance that the AEDs should be selected based on their high anticonvulsant properties, as well as a high level of neuroprotection and minimal side effects. For the last several years many researchers focused their efforts on looking for new potent natu ral and synthetic anticonvulsants. Results from studies of some natu ral cannabinoid compounds as well as synthetic cannabinoids clearly prove the anticonvulsive properties of these substances in various in vitro and in vivo models of epilepsy. This review summarizes the latest experimental data concerning the potential significance of the endoge nous cannabinoid system and cannabinoids in the treatment of epilepsy.