Novel anticonvulsant medications in development.
Epilepsy is currently the most prevalent neurological disorder worldwide. Pharmacological therapy remains the cornerstone of epilepsy treatment, however, refractory epilepsy is still a significant clinical problem despite the release of the second generation of anticonvulsants. Anticonvulsant treatment failures may result from lack of efficacy and presence of significant side effects. One rationale for incomplete effectiveness of the currently available anticonvulsants is that they were identified using the same classical models and therefore work largely by the same actions. These mechanisms fail to consider variations in the pathophysiological process that results in epilepsy, nor have they been shown to prevent the process of developing epilepsy (epileptogenesis). The next generation of anticonvulsants has taken into account the shortcomings of existing agents and attempted to improve on the currently available treatments using rationale drug design. This group of investigational anticonvulsants may be broadly classified as possessing one or more of the following: 1) increased tolerability through improvement in drug chemical structure or better delivery to the site of action, 2) new mechanisms (or combinations of mechanisms) of action, 3) improved pharmacokinetic properties. This article will discuss the next generation of anticonvulsants (carabersat, CGX-1007, fluorofelbamate, harkoseride, losigamone, pregabalin, retigabine, safinamide, SPD-421, talampanel, valrocemide) and the possible populations in which they would be clinically useful.
Hovinga
Collin A
CA
Department of Pharmacy, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA. hovingc@ccf.org
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000494:pharmacology; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D015918:Infusion Pumps, Implantable / Q000639:trends; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods / Q000639:trends*
D000927:Anticonvulsants; D007473:Ion Channels