Lamotrigine inhibits Ca2+ currents in cortical neurons: functional implications.
In pyramidal cortical cells, high-voltage-activated Ca2+ currents affect seizure propagation and the release of excitatory amino acids at the corticostriatal axon terminals. The new antiepileptic drug lamotrigine (Lamictal) produced a large and dose-dependent inhibition of high-voltage-activated Ca2+ currents (IC50 = 12.3 microM) in rat cortical neurons. This action was not blocked by the dihydropyridine receptor antagonist nifedipine; instead, the response was blocked by the concomitant application of the N-type Ca2+ channel blocker, omega-conotoxin GVIA (1-3 microM) 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 excitatory amino acid release in the corticostriatal pathway, partially explaining lamotrigine usefulness in the therapy of epilepsy as well as in the treatment of excitatory amino acid-induced neurotoxicity.
Stefani
A
A
Dipartimento Sanità Pubblica, Università di Tor Vergata, Rome, Italy.
Spadoni
F
F
Siniscalchi
A
A
Bernardi
G
G
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D000077213:Lamotrigine; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D014227:Triazines / Q000494:pharmacology*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014227:Triazines; D009543:Nifedipine; D000077213:Lamotrigine