Why are antiepileptic drugs used for nonepileptic conditions?
In: Epilepsia (Series 4), 2012-11-03, S. 26-33
Online
academicJournal
Zugriff:
Antiepileptic drugs (AEDs) are used to treat vari-ous nonepileptic central nervous system (CNS) disorders, both in neurology and psychiatry. Most AEDs have multiple mechanisms of action (MOAs), which include modulation of ]>-aminobu-tyric acid (GABA)ergic and glutamatergic neuro-transmission, and alteration of voltage-gated ion channels or intracellular signaling pathways. These MOAs may explain the efficacy of AEDs in the treatment of bipolar disorder and neuropath-ic pain. Bipolar disorder and epilepsy have some common features, such as their episodic nature and associated kindling phenomena, which led to the regulatory approval and use of the AEDs car-bamazepine (CBZ), valproic acid (VPA), and lamotrigine (LTG) in the treatment of bipolar dis-order. A major limitation for the development of drugs with improved mood-stabilizing activity is the lack of knowledge on the mechanism of treat-ment for bipolar disorder. In contrast to epilepsy, no animal models in bipolar disorder are univer-sally accepted and no model is able to exhibit the characteristic mood swings. Although most AEDs have now been investigated for their mood-stabi-lizing effects, only three (e.g., VPA, CBZ, and LTG) demonstrated clinical efficacy in patients. This suggests that the mechanism of drug action in mood disorder and in epilepsy only partially overlaps. Peripheral nerve damage leads to the initiation of cellular and molecular changes in the nervous system resulting in ectopic, repetitive fir-ing perceived as chronic pain. Epileptic seizures are also characterized by hyperexcitability of neu-rons in the brain. The spontaneous electrogenesis in neuropathic pain has similarities to that of epi-lepsy. Alteration in sodium channels expression suggests that the mechanism underlying epileptic hyperexcitability may be similar to those underly-ing neuropathic pain. The AEDs gabapentin (GBP) and pregabalin (PGB) have become the mainstay of treatment for various neuropathic pain syndromes, owing to their ability to inhibit neuronal hyperactivity along the pain pathways. One explanation for how GBP and PGB relieve neuropathic pain is that they bind selectively to the Ca+2-channel subunit α2-δ in muscle tissue and brain. With 16 new AEDs having entered the market since 1990 the antiepileptic market is crowded. Consequently, epilepsy alone is not attractive in 2012 to the pharmaceutical industry, even though the clinical needs of refractory epi-lepsy remain unmet. Due to this situation, the future design of new AEDs must also include a potential in nonepileptic CNS disorders, such as bipolar disorder and neuropathic pain. The global market size of each of these two indications is similar to that of epilepsy, whereas they both cur-rently have fewer approved drugs for treatment than epilepsy. Therefore, a new AED with addi-tional approved indications in bipolar disorder and neuropathic pain might have a potential mar-ket size three times larger than that of epilepsy alone. [ABSTRACT FROM AUTHOR]
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Why are antiepileptic drugs used for nonepileptic conditions?
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Autor/in / Beteiligte Person: | Bialer, Meir |
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Zeitschrift: | Epilepsia (Series 4), 2012-11-03, S. 26-33 |
Veröffentlichung: | 2012 |
Medientyp: | academicJournal |
ISSN: | 0013-9580 (print) |
DOI: | 10.1111/j.1528-1167.2012.03712.x |
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