Lamotrigine and carbamazepine affect differently the release of D-[3H]aspartate from mouse cerebral cortex slices: involvement of NO.
The effects of lamotrigine and carbamazepine on the release of preloaded D-[3H]aspartate and the involvement of nitric oxide were studied with mouse cerebral cortical slices in a superfusion system. Lamotrigine inhibited the veratridine-evoked release, whereas the K+-stimulated release was attenuated more strongly by carbamazepine than by lamotrigine. These effects were accentuated by the N-methyl-D-aspartate receptor antagonist L-2-amino-5-phosphonovalerate and the nitric oxide synthase inhibitor L-nitroarginine, but diminished by the nitric oxide donor sodium nitroprusside. The results show that in addition to the blockade of voltage-sensitive Na+ (and Ca2+) channels, NO-mediated mechanisms are probably involved in the anticonvulsant actions of carbamazepine and, in particular, those of lamotrigine.
Afanas'ev
I
I
Department of Pharmacology, Russian Academy of Medical Sciences, Moscow.
Kudrin
V
V
Rayevsky
K S
KS
Varga
V
V
Saransaari
P
P
Oja
S S
SS
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002220:Carbamazepine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D000077213:Lamotrigine; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology*; D014316:Tritium
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D014227:Triazines; D014316:Tritium; D019335:Nitroarginine; D001224:Aspartic Acid; D009569:Nitric Oxide; D002220:Carbamazepine; D015763:2-Amino-5-phosphonovalerate; D019001:Nitric Oxide Synthase; D000077213:Lamotrigine