Mechanisms of action of new antiepileptic drugs: rational design and serendipitous findings.
After years without any major breakthroughs in the treatment of epilepsy disorders, a new wave of antiepileptic drugs have become available to clinicians. Felbamate, gabapentin, lamotrigine and vigabatrin are among the most promising of this new generation of drugs and, when used as add-on therapy, provide some improvement in a significant number of patients suffering from previously refractory epilepsy whilst exhibiting a lower risk of unwanted side-effects than traditional antiepileptic drugs. In this article, Neil Upton reviews the recent discoveries that suggest these four new agents exert their antiepileptic properties by acting through diverse and often novel mechanisms, some of which are by design, and some of which are by chance. Also highlighted are examples of the most innovative mechanistic approaches currently being adopted to produce the next generation of antiepileptic drugs.
Upton
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Department of Psychiatry Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
D000085:Acetates / Q000494:pharmacology; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids; D000078328:Felbamate; D000077206:Gabapentin; D006801:Humans; D000077213:Lamotrigine; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D048448:Phenylcarbamates; D011409:Propylene Glycols; D014227:Triazines; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020888:Vigabatrin; D000077213:Lamotrigine; D000078328:Felbamate