Document Detail

Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled seizures: cross-tolerance to carbamazepine but not valproate or diazepam.
MedLine Citation:
PMID:  10739634     Owner:  NLM     Status:  MEDLINE    
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.
E Krupp; T Heynen; X L Li; R M Post; S R Weiss
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental neurology     Volume:  162     ISSN:  0014-4886     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-23     Completed Date:  2000-05-23     Revised Date:  2013-08-21    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  278-89     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
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MeSH Terms
Amygdala / drug effects*,  physiopathology
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
Rats, Sprague-Dawley
Seizures / drug therapy,  metabolism*
Triazines / administration & dosage,  pharmacology*
Valproic Acid / administration & dosage,  pharmacology
Reg. No./Substance:
0/Anticonvulsants; 0/Triazines; 298-46-4/Carbamazepine; 439-14-5/Diazepam; 99-66-1/Valproic Acid; U3H27498KS/lamotrigine

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