LAMOTRIGINE INHIBITS CA2-NEURONS - FUNCTIONAL IMPLICATIONS( CURRENTS IN CORTICAL)

In pyramidal cortical cells, high-voltage-activated Ca2+ currents affe ct seizure propagation and the release of excitatory amino acids at th e corticostriatal axon terminals. The new antiepileptic drug lamotrigi ne (Lamictal) produced a large and dose-dependent inhibition of high-v oltage-activated Ca2+ currents (IC50 = 12.3 mu M) in rat cortical neur ons. This action was not blocked by the dihydropyridine receptor antag onist nifedipine; instead, the response was blocked by the concomitant application of the N-type Ca2+ channel blocker, omega-conotoxin GVIA (1-3 mu M) and the P-type Ca2+ channel blocker, omega-agatoxin-IVA (20 -100 nM). These findings demonstrate that lamotrigine, at therapeutic doses, is capable of modulating the Ca2+ conductances involved in exci tatory amino acid release in the corticostriatal pathway, partially ex plaining lamotrigine usefulness in the therapy of epilepsy as well as in the treatment of excitatory amino acid-induced neurotoxicity.