Accumulating experimental data suggests a number of successful drug targets against epilepsy which eventually failed in the clinical setup. Mammalian target of rapamycin inhibitors, multi-drug resistance transporter inhibitors, cyclo-oxygenase-2 inhibitors, statins, etc. are the most promising and well studied among them. Drugs aiming at these targets produced beneficial response in most of the in vitro and in vivo seizure models. However, in certain situations, they have produced differential rather controversial results. Their effects varied with the seizure model, species, time and route of administration, different drugs from the same class, etc. This review emphasises on such drugs which presented with variability in their beneficial effects against seizures and epilepsy. This review critically summarises the preclinical evidence of these targets in the context of seizures and the probable reasons for their variability and clinical failures.
Keywords: COX-2 inhibitors; P-gp inhibitors; mTOR inhibitors; refractory epilepsy; statins.