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Article: Unidirectional Cross-tolerance from Levetiracetam to Carbamazepine in Amygdala-kindled Seizures

TitleUnidirectional Cross-tolerance from Levetiracetam to Carbamazepine in Amygdala-kindled Seizures
Authors
Issue Date2003
PublisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.epilepsia.com/
Citation
Epilepsia, 2003, v. 44 n. 12, p. 1487-1493 How to Cite?
AbstractPurpose: Tolerance is a potential problem in long-term anticonvulsant therapy of epilepsy, bipolar disorder, and neuropathic pain. The present study was designed to determine whether cross-tolerance occurs between levetiracetam (LEV) and carbamazepine (CBZ) in amygdala-kindled rats. Methods: Male Sprague-Dawley rats were implanted with an electrode into the left amygdala. While kindling stimulation was started, animals received repeated treatment (i.p.) with saline (n = 7) or LEV (150 mg/kg, n = 8). Saline-injected rats were subsequently challenged with a single dose of 150 mg/kg LEV when full kindling developed (stage >4). Both groups of rats were then administered long-term CBZ (5 mg/kg) until rats developed complete tolerance. All CBZ-tolerant rats were subsequently reexposed to LEV (150 mg/kg) for an additional 10 consecutive days. Results: Repeated LEV treatment significantly suppressed the increase in seizure stage, seizure duration, and afterdischarge duration induced by amygdala stimulation, markedly increasing the number of stimulations to achieve a kindling major motor seizure. The LEV challenge produced a more robust suppression of seizure stage in saline-injected rats compared with LEV-treated animals. CBZ treatment markedly suppressed fully kindled seizures in rats initially injected with saline, and then anticonvulsant tolerance rapidly developed after 3-4 days of repeated treatment. In contrast, rats that had initially received repeated LEV treatment did not show a response to treatment with CBZ (5 mg/kg). When CBZ-tolerant rats were subsequently exposed to LEV (150 mg/kg), noticeable anticonvulsant effects were observed; but these were gradually lost with increasing numbers of LEV exposures. Conclusions: Whereas LEV shows potent antiepileptogenic and anticonvulsant effects in amygdala-kindled rats, its repeated treatment induces anticonvulsant tolerance and unidirectional cross-tolerance to CBZ. In contrast, anticonvulsant tolerance to CBZ does not transfer to LEV. The mechanistic implications of the present results for clinical therapeutics remain to be evaluated.
Persistent Identifierhttp://hdl.handle.net/10722/179418
ISSN
2015 Impact Factor: 4.706
2015 SCImago Journal Rankings: 2.579
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, ZJen_US
dc.contributor.authorXing, GQen_US
dc.contributor.authorRussell, Sen_US
dc.contributor.authorObeng, Ken_US
dc.contributor.authorPost, RMen_US
dc.date.accessioned2012-12-19T09:56:19Z-
dc.date.available2012-12-19T09:56:19Z-
dc.date.issued2003en_US
dc.identifier.citationEpilepsia, 2003, v. 44 n. 12, p. 1487-1493en_US
dc.identifier.issn0013-9580en_US
dc.identifier.urihttp://hdl.handle.net/10722/179418-
dc.description.abstractPurpose: Tolerance is a potential problem in long-term anticonvulsant therapy of epilepsy, bipolar disorder, and neuropathic pain. The present study was designed to determine whether cross-tolerance occurs between levetiracetam (LEV) and carbamazepine (CBZ) in amygdala-kindled rats. Methods: Male Sprague-Dawley rats were implanted with an electrode into the left amygdala. While kindling stimulation was started, animals received repeated treatment (i.p.) with saline (n = 7) or LEV (150 mg/kg, n = 8). Saline-injected rats were subsequently challenged with a single dose of 150 mg/kg LEV when full kindling developed (stage >4). Both groups of rats were then administered long-term CBZ (5 mg/kg) until rats developed complete tolerance. All CBZ-tolerant rats were subsequently reexposed to LEV (150 mg/kg) for an additional 10 consecutive days. Results: Repeated LEV treatment significantly suppressed the increase in seizure stage, seizure duration, and afterdischarge duration induced by amygdala stimulation, markedly increasing the number of stimulations to achieve a kindling major motor seizure. The LEV challenge produced a more robust suppression of seizure stage in saline-injected rats compared with LEV-treated animals. CBZ treatment markedly suppressed fully kindled seizures in rats initially injected with saline, and then anticonvulsant tolerance rapidly developed after 3-4 days of repeated treatment. In contrast, rats that had initially received repeated LEV treatment did not show a response to treatment with CBZ (5 mg/kg). When CBZ-tolerant rats were subsequently exposed to LEV (150 mg/kg), noticeable anticonvulsant effects were observed; but these were gradually lost with increasing numbers of LEV exposures. Conclusions: Whereas LEV shows potent antiepileptogenic and anticonvulsant effects in amygdala-kindled rats, its repeated treatment induces anticonvulsant tolerance and unidirectional cross-tolerance to CBZ. In contrast, anticonvulsant tolerance to CBZ does not transfer to LEV. The mechanistic implications of the present results for clinical therapeutics remain to be evaluated.en_US
dc.languageengen_US
dc.publisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.epilepsia.com/en_US
dc.relation.ispartofEpilepsiaen_US
dc.subject.meshAmygdala - Drug Effectsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnticonvulsants - Pharmacologyen_US
dc.subject.meshCarbamazepine - Pharmacologyen_US
dc.subject.meshDrug Toleranceen_US
dc.subject.meshElectroencephalography - Drug Effectsen_US
dc.subject.meshInjections, Intraperitonealen_US
dc.subject.meshKindling, Neurologic - Drug Effectsen_US
dc.subject.meshLong-Term Careen_US
dc.subject.meshMaleen_US
dc.subject.meshPiracetam - Analogs & Derivatives - Pharmacologyen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.titleUnidirectional Cross-tolerance from Levetiracetam to Carbamazepine in Amygdala-kindled Seizuresen_US
dc.typeArticleen_US
dc.identifier.emailZhang, ZJ: zhangzj@hkucc.hku.hken_US
dc.identifier.authorityZhang, ZJ=rp01297en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.0013-9580.2003.34803.xen_US
dc.identifier.pmid14636317-
dc.identifier.scopuseid_2-s2.0-0347364700en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0347364700&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume44en_US
dc.identifier.issue12en_US
dc.identifier.spage1487en_US
dc.identifier.epage1493en_US
dc.identifier.isiWOS:000187424700002-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridZhang, ZJ=8061473900en_US
dc.identifier.scopusauthoridXing, GQ=7103115617en_US
dc.identifier.scopusauthoridRussell, S=7401538133en_US
dc.identifier.scopusauthoridObeng, K=6701594477en_US
dc.identifier.scopusauthoridPost, RM=7202218145en_US

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