Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled seizures : Cross-tolerance to carbamazepine but not valproate or diazepam
In: Experimental neurology (Print), Jg. 162 (2000), Heft 2, S. 278-289
academicJournal
- print, 58 ref
Zugriff:
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.
Titel: |
Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled seizures : Cross-tolerance to carbamazepine but not valproate or diazepam
|
---|---|
Autor/in / Beteiligte Person: | KRUPP, E ; HEYNEN, T ; LI, X.-L ; POST, R. M ; WEISS, S. R. B |
Link: | |
Zeitschrift: | Experimental neurology (Print), Jg. 162 (2000), Heft 2, S. 278-289 |
Veröffentlichung: | Amsterdam: Elsevier, 2000 |
Medientyp: | academicJournal |
Umfang: | print, 58 ref |
ISSN: | 0014-4886 (print) |
Schlagwort: |
|
Sonstiges: |
|