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- Publisher Website: 10.1111/j.0013-9580.2003.34803.x
- Scopus: eid_2-s2.0-0347364700
- PMID: 14636317
- WOS: WOS:000187424700002
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Article: Unidirectional Cross-tolerance from Levetiracetam to Carbamazepine in Amygdala-kindled Seizures
Title | Unidirectional Cross-tolerance from Levetiracetam to Carbamazepine in Amygdala-kindled Seizures |
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Authors | |
Keywords | Carbamazepine Cross-tolerance Kindling Levetiracetam Rat |
Issue Date | 2003 |
Publisher | Wiley-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? |
Abstract | Purpose: 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 Identifier | http://hdl.handle.net/10722/179418 |
ISSN | 2023 Impact Factor: 6.6 2023 SCImago Journal Rankings: 2.227 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
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dc.contributor.author | Zhang, ZJ | en_US |
dc.contributor.author | Xing, GQ | en_US |
dc.contributor.author | Russell, S | en_US |
dc.contributor.author | Obeng, K | en_US |
dc.contributor.author | Post, RM | en_US |
dc.date.accessioned | 2012-12-19T09:56:19Z | - |
dc.date.available | 2012-12-19T09:56:19Z | - |
dc.date.issued | 2003 | en_US |
dc.identifier.citation | Epilepsia, 2003, v. 44 n. 12, p. 1487-1493 | en_US |
dc.identifier.issn | 0013-9580 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/179418 | - |
dc.description.abstract | Purpose: 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.language | eng | en_US |
dc.publisher | Wiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.epilepsia.com/ | en_US |
dc.relation.ispartof | Epilepsia | en_US |
dc.subject | Carbamazepine | - |
dc.subject | Cross-tolerance | - |
dc.subject | Kindling | - |
dc.subject | Levetiracetam | - |
dc.subject | Rat | - |
dc.subject.mesh | Amygdala - Drug Effects | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Anticonvulsants - Pharmacology | en_US |
dc.subject.mesh | Carbamazepine - Pharmacology | en_US |
dc.subject.mesh | Drug Tolerance | en_US |
dc.subject.mesh | Electroencephalography - Drug Effects | en_US |
dc.subject.mesh | Injections, Intraperitoneal | en_US |
dc.subject.mesh | Kindling, Neurologic - Drug Effects | en_US |
dc.subject.mesh | Long-Term Care | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Piracetam - Analogs & Derivatives - Pharmacology | en_US |
dc.subject.mesh | Rats | en_US |
dc.subject.mesh | Rats, Sprague-Dawley | en_US |
dc.title | Unidirectional Cross-tolerance from Levetiracetam to Carbamazepine in Amygdala-kindled Seizures | en_US |
dc.type | Article | en_US |
dc.identifier.email | Zhang, ZJ: zhangzj@hkucc.hku.hk | en_US |
dc.identifier.authority | Zhang, ZJ=rp01297 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1111/j.0013-9580.2003.34803.x | en_US |
dc.identifier.pmid | 14636317 | - |
dc.identifier.scopus | eid_2-s2.0-0347364700 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-0347364700&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 44 | en_US |
dc.identifier.issue | 12 | en_US |
dc.identifier.spage | 1487 | en_US |
dc.identifier.epage | 1493 | en_US |
dc.identifier.isi | WOS:000187424700002 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Zhang, ZJ=8061473900 | en_US |
dc.identifier.scopusauthorid | Xing, GQ=7103115617 | en_US |
dc.identifier.scopusauthorid | Russell, S=7401538133 | en_US |
dc.identifier.scopusauthorid | Obeng, K=6701594477 | en_US |
dc.identifier.scopusauthorid | Post, RM=7202218145 | en_US |
dc.identifier.issnl | 0013-9580 | - |