| Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled seizures: cross-tolerance to carbamazepine but not valproate or diazepam. | |
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MedLine Citation:
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PMID: 10739634 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Using an amygdala-kindled seizure paradigm, we evaluated the acute and chronic anticonvulsant effects of lamotrigine (LTG). Lamotrigine produced dose-dependent inhibitory effects on seizure stage, afterdischarge (AD), and seizure duration. Lamotrigine (15 mg/kg) also increased the afterdischarge and seizure thresholds. Following repeated LTG administration and stimulation at 48-h intervals, tolerance developed to LTG's (15 mg/kg) anticonvulsant effects, and cross-tolerance was observed to the anticonvulsant effects of carbamazepine (CBZ, 15 mg/kg). In a separate group of kindled rats, CBZ (15 mg/kg) was repeatedly administered to induce tolerance. This led to a partial cross-tolerance to LTG, manifesting as an increased rate of tolerance development to LTG, and seizures following the first injection in some animals, which were not observed in CBZ-nontolerant controls. When these rats were made fully tolerant to LTG and then exposed to higher doses of LTG (30 and 50 mg/kg), no anticonvulsant effects were observed. In contrast, higher doses of CBZ (30 mg/kg) did restore efficacy in CBZ-tolerant animals. Cross-tolerance from LTG to valproate and diazepam was not observed, although cross-tolerance from CBZ to valproate has been reported previously. These data suggest that LTG has both shared and distinct anticonvulsant mechanisms from those of CBZ on amygdala-kindled seizures. The implications of these results for clinical therapeutics remain to be evaluated. |
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Authors:
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E Krupp; T Heynen; X L Li; R M Post; S R Weiss |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental neurology Volume: 162 ISSN: 0014-4886 ISO Abbreviation: Exp. Neurol. Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-05-23 Completed Date: 2000-05-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370712 Medline TA: Exp Neurol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 278-89 Citation Subset: IM |
Copyright Information:
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Copyright 2000 Academic Press. |
Affiliation:
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Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amygdala
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drug effects*,
physiopathology Animals Anticonvulsants / administration & dosage, pharmacology* Carbamazepine / administration & dosage, pharmacology* Diazepam / administration & dosage, pharmacology Disease Models, Animal Dose-Response Relationship, Drug Drug Interactions Drug Tolerance* Electric Stimulation Electrodes, Implanted Kindling, Neurologic / drug effects Male Rats Rats, Sprague-Dawley Seizures / drug therapy, metabolism* Triazines / administration & dosage, pharmacology* Valproic Acid / administration & dosage, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Anticonvulsants; 0/Triazines; 298-46-4/Carbamazepine; 439-14-5/Diazepam; 84057-84-1/lamotrigine; 99-66-1/Valproic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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