TY - JOUR
T1 - Critical re-evaluation of previous preclinical strategies for the discovery and the development of new antiepileptic drugs
AU - Löscher, W.
AU - Leppik, I. E.
PY - 2002
Y1 - 2002
N2 - During the last decade, several new antiepileptic drugs (AEDs) have been introduced in Europe, the United States, or other parts of the world. Although the antiepileptic efficacy of these drugs is not superior to that of older AEDs, some of the new drugs offer advantages in terms of improved tolerability, ease of use, and reduced interaction potential with other drugs. However, the new AEDs have only a modest impact on patients with refractory epilepsies, so that about one third of patients with epilepsy continue to have seizures with current pharmacotherapies. Thus, there is a continuing need for new medical therapies in epilepsy. During the Workshop on "New Horizons in the Development of Antiepileptic Drugs" (November 28-29, 2001, Philadelphia, PA), one topic dealt with the critical re-evaluation of previous preclinical strategies for the discovery and the development of new AEDs. The discussion of this session, which was chaired by the authors, is summarized in this article. Main issues of the discussion were whether epilepsy is a progressive disease and whether refractory epilepsy is preventable, the use of acute versus chronic animal models in the discovery and development of new AEDs, models for drug-resistant epilepsy, mechanisms of drug resistance, alterations in adverse effect potential of AEDs by epilepsy, and advances in pharmacogenomics and our understanding of pharmacologic responsiveness in epilepsy. Overall, it was felt that the current preclinical strategies for the discovery and development of new AEDs have to be redefined in order to identify agents that are clearly superior to current medications.
AB - During the last decade, several new antiepileptic drugs (AEDs) have been introduced in Europe, the United States, or other parts of the world. Although the antiepileptic efficacy of these drugs is not superior to that of older AEDs, some of the new drugs offer advantages in terms of improved tolerability, ease of use, and reduced interaction potential with other drugs. However, the new AEDs have only a modest impact on patients with refractory epilepsies, so that about one third of patients with epilepsy continue to have seizures with current pharmacotherapies. Thus, there is a continuing need for new medical therapies in epilepsy. During the Workshop on "New Horizons in the Development of Antiepileptic Drugs" (November 28-29, 2001, Philadelphia, PA), one topic dealt with the critical re-evaluation of previous preclinical strategies for the discovery and the development of new AEDs. The discussion of this session, which was chaired by the authors, is summarized in this article. Main issues of the discussion were whether epilepsy is a progressive disease and whether refractory epilepsy is preventable, the use of acute versus chronic animal models in the discovery and development of new AEDs, models for drug-resistant epilepsy, mechanisms of drug resistance, alterations in adverse effect potential of AEDs by epilepsy, and advances in pharmacogenomics and our understanding of pharmacologic responsiveness in epilepsy. Overall, it was felt that the current preclinical strategies for the discovery and development of new AEDs have to be redefined in order to identify agents that are clearly superior to current medications.
KW - Adverse effects
KW - Animal models
KW - Drug-resistance
KW - Epilepsy
KW - P-glycoprotein
KW - Progression
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U2 - 10.1016/S0920-1211(02)00064-5
DO - 10.1016/S0920-1211(02)00064-5
M3 - Article
C2 - 12151113
AN - SCOPUS:0036347770
SN - 0920-1211
VL - 50
SP - 17
EP - 20
JO - Epilepsy Research
JF - Epilepsy Research
IS - 1-2
ER -