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Chemical properties of antiepileptic drugs (AEDs).
Adv Drug Deliv Rev 2012; 64(10):887-95AD

Abstract

Between 1990 and 2011 the following fifteen new antiepileptic drugs (AEDs) were approved: eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. These AEDs (except felbamate) offer appreciable advantages in terms of their favorable pharmacokinetics, improved tolerability and lower potential for drug interactions. All AEDs introduced after 1990 that are not second generation drugs (with the exception of vigabatrin and tiagabine) were developed empirically (sometimes serendipitously) utilizing mechanism-unbiased anticonvulsant animal models. The empirical nature of the discovery of new AEDs in the last three decades coupled with their multiple mechanisms of action explains their diverse chemical structures. The availability of old and new AEDs with various activity spectra and different tolerability profiles enables clinicians to better tailor drug choice to the characteristics of individual patients. With fifteen new AEDs having entered the market in the past 20years the antiepileptic market is crowded. Consequently, epilepsy alone is not attractive in 2011 to the pharmaceutical industry even though the clinical need of refractory epilepsy remains unmet. Due to this situation, future design of new AEDs must also have a potential in non-epileptic CNS disorders such as neuropathic pain, migraine prophylaxis and bipolar disorder or fibromyalgia as demonstrated by the sales revenues of pregabalin, topiramate and valproic acid. This review analyzes the effect that the emerging knowledge on the chemical properties of the old AEDs starting from phenobarbital (1912) has had on the design of subsequent AEDs and new therapeutics as well as the current approach to AED discovery.

Authors+Show Affiliations

School of Pharmacy, Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel. bialer@md.huji.ac.il

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

22210279

Citation

Bialer, Meir. "Chemical Properties of Antiepileptic Drugs (AEDs)." Advanced Drug Delivery Reviews, vol. 64, no. 10, 2012, pp. 887-95.
Bialer M. Chemical properties of antiepileptic drugs (AEDs). Adv Drug Deliv Rev. 2012;64(10):887-95.
Bialer, M. (2012). Chemical properties of antiepileptic drugs (AEDs). Advanced Drug Delivery Reviews, 64(10), pp. 887-95. doi:10.1016/j.addr.2011.11.006.
Bialer M. Chemical Properties of Antiepileptic Drugs (AEDs). Adv Drug Deliv Rev. 2012;64(10):887-95. PubMed PMID: 22210279.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chemical properties of antiepileptic drugs (AEDs). A1 - Bialer,Meir, Y1 - 2011/11/21/ PY - 2011/07/14/received PY - 2011/11/07/revised PY - 2011/11/14/accepted PY - 2012/1/3/entrez PY - 2012/1/3/pubmed PY - 2012/10/26/medline SP - 887 EP - 95 JF - Advanced drug delivery reviews JO - Adv. Drug Deliv. Rev. VL - 64 IS - 10 N2 - Between 1990 and 2011 the following fifteen new antiepileptic drugs (AEDs) were approved: eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. These AEDs (except felbamate) offer appreciable advantages in terms of their favorable pharmacokinetics, improved tolerability and lower potential for drug interactions. All AEDs introduced after 1990 that are not second generation drugs (with the exception of vigabatrin and tiagabine) were developed empirically (sometimes serendipitously) utilizing mechanism-unbiased anticonvulsant animal models. The empirical nature of the discovery of new AEDs in the last three decades coupled with their multiple mechanisms of action explains their diverse chemical structures. The availability of old and new AEDs with various activity spectra and different tolerability profiles enables clinicians to better tailor drug choice to the characteristics of individual patients. With fifteen new AEDs having entered the market in the past 20years the antiepileptic market is crowded. Consequently, epilepsy alone is not attractive in 2011 to the pharmaceutical industry even though the clinical need of refractory epilepsy remains unmet. Due to this situation, future design of new AEDs must also have a potential in non-epileptic CNS disorders such as neuropathic pain, migraine prophylaxis and bipolar disorder or fibromyalgia as demonstrated by the sales revenues of pregabalin, topiramate and valproic acid. This review analyzes the effect that the emerging knowledge on the chemical properties of the old AEDs starting from phenobarbital (1912) has had on the design of subsequent AEDs and new therapeutics as well as the current approach to AED discovery. SN - 1872-8294 UR - https://www.unboundmedicine.com/medline/citation/22210279/Chemical_properties_of_antiepileptic_drugs__AEDs__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0169-409X(11)00286-9 DB - PRIME DP - Unbound Medicine ER -