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INTRODUCTION
Three well-known antiepileptic drugs, carbamazepine, lamotrigine and valproate, were evaluated in different tests of epilepsy in the mouse and in the
rat. These substances were compared in two models used to assess generalized tonic-clonic seizures, the audiogenic seizure test in the DBA/2 mouse
and the maximal electroshock (MES) test in the rat as well as in the amygdala kindling test in the rat considered as a model of partial seizures with
secondary generalization.
RESULTS
Audiogenic Seizure Test in the mouse MES Test in the rat Amygdala Kindling Test in the rat
Vehicle
Numberr of tonic convulsions
Wild Running Clonic convulsions Tonic convulsions Death 6 Valproate (150 mg/kg)
12
10 Valproate (300 mg/kg)
9 5
10
Number of rats
Seizure score
4
7 8
6
6 3
5
*
4 2
4 ***
3 *
***
N
2 2 1 *
***
1
***
**
0 0 0
Vehicle Valproate Valproate Valproate Vehicle Valproate Valproate Valproate -24 h + 30 min + 90 min +180 min +6h
(20 mg/kg) (60 mg/kg) (180 mg/kg) (75 mg/kg) (150 mg/kg) 300 (mg/kg)
Vehicle
Number of tonic convulsions
Wild running Clonic convulsions Tonic convulsions Death 6 Carbamazepine (250 mg/kg)
10 12 Carbamazepine (500 mg/kg)
9 5
10
Number of rats
Seizure score
8
4
7 8
6
3
*
5 6 **
**
4
**
**
2
***
3 4
2 *** 1
2 ***
1
**
**
*
0 0 0
Vehicle Carbamazepine Carbamazepine Carbamazepine Vehicle Carbamazepine Carbamazepine Carbamazepine -24 h +1h +2h + 24 h
(6.25 mg/kg) (12.5 mg/kg) (25 mg/kg) (12.5 mg/kg) (25 mg/kg) (50 mg/kg)
Vehicle
6 Lamotrigine (4 mg/kg)
Number of tonic convulsions
Wild Running Clonic convulsions Tonic convulsions Death 12 Lamotrigine (16 mg/kg)
10 5
9 10
Number of rats
Seizure score
8 4
7 8
6 3
6 **
5
4 4 2
3
***
***
2 2 *** *** 1
***
1 * *
0 0 0
Vehicle Lamotrigine Lamotrigine Lamotrigine Vehicle Lamotrigine Lamotrigine Lamotrigine -24 h +1h +2h + 24 h
(4 mg/kg) (8 mg/kg) (16 mg/kg) (4 mg/kg) (8 mg/kg) (16 mg/kg)
Fisher’s Exact Test: *, p < 0.05, **, p < 0.01 and ***: p < 0.001. Fisher’s Exact Test: **, p < 0.01 and ***: p < 0.001. Wilcoxon Test: *, p < 0.05 and **: p < 0.01.
Valproate (180 mg/kg), Carbamazepine (12.5-25 mg/kg) Valproate (150-300 mg/kg), Carbamazepine (12.5-50 Valproate (300 mg/kg) decreased the seizure score at 30
and Lamotrigine (4-16 mg/kg) suppressed tonic convulsions mg/kg) and Lamotrigine (4-16 mg/kg) dose- and 90 minutes. Similar effects were observed with
and protected from death. Clonic convulsions were also dependently decreased tonic convulsions. Carbamazepine (500 mg/kg) at 1, 2 and 24 hours. No
decreased. significant effects were observed with Lamotrigine at 4 or 16
mg/kg. © Porsolt – All rights reserved.
CONCLUSION
The results show that the active doses of carbamazepine, lamotrigine and valproate vary depending on the epilepsy model. Partial
seizures with secondary generalization are antagonized after administration of these substances at higher dose strengths as compared
with generalized seizures, confirming the importance of testing the same compound across several tests to assess anti-convulsant
efficacy.
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