The effect of lamotrigine upon development of cortical kindled seizures in the rat.
The effect of lamotrigine, a novel potential antiepileptic drug, upon the development of kindled cortical seizures was investigated in rats. Although lamotrigine, at all doses tested, failed to block or reduce the rate of development of kindling, it did have a profound effect upon the production of both non-kindled and kindled responses. All doses (3, 6, 12 and 18 mg/kg) produced a significant increase in the number of nil responses (where stimulation failed to evoke a behavioural clonus or afterdischarge) and a decrease in non-kindled responses. Doses of 12 and 18 mg/kg also significantly reduced the number of kindled responses and the duration of the kindled seizure. It is suggested that these effects of lamotrigine result from its ability to inhibit the release of glutamate, an excitatory amino acid which has been implicated in the production of kindled seizures. In contrast to previous studies on the development of kindling, it was found that in the groups which received either 12 or 18 mg/kg lamotrigine, it was possible to produce kindling without evoking any nonkindled afterdischarge. This finding is discussed in the light of the current theories surrounding the kindling process. This study suggests that lamotrigine, as well as possibly being of value in the treatment of complex partial and generalised (tonic-clonic) seizures, may also be of value in the treatment of elementary (simple) partial seizures.
O'Donnell
R A
RA
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Miller
A A
AA
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D004558:Electric Stimulation; D004569:Electroencephalography; D007696:Kindling, Neurologic / Q000187:drug effects*; D000077213:Lamotrigine; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000503:physiopathology*; D014227:Triazines / Q000494:pharmacology*
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine