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Titolo:
Electrophysiology of sipatrigine: A lamotrigine derivative exhibiting neuroprotective effects
Autore:
Calabresi, P; Stefani, A; Marfia, GA; Hainsworth, AH; Centonze, D; Saulle, E; Spadoni, F; Leach, MJ; Giacomini, P; Bernardi, G;
Indirizzi:
Univ Roma Tor Vergata, Dipartimento Neurosci, Neurol Clin, I-00133 Rome, Italy Univ Roma Tor Vergata Rome Italy I-00133 eurol Clin, I-00133 Rome, Italy IRCCS, Osped Santa Lucia, Rome, Italy IRCCS Rome ItalyIRCCS, Osped Santa Lucia, Rome, Italy De Montfort Univ, Sch Pharm, Leicester LE1 9BH, Leics, England De MontfortUniv Leicester Leics England LE1 9BH LE1 9BH, Leics, England Univ Greenwich, Sch Life Sci, London SE18 6PF, England Univ Greenwich London England SE18 6PF ife Sci, London SE18 6PF, England Univ La Sapienza, Neurol Clin 2, Rome, Italy Univ La Sapienza Rome Italy niv La Sapienza, Neurol Clin 2, Rome, Italy
Titolo Testata:
EXPERIMENTAL NEUROLOGY
fascicolo: 1, volume: 162, anno: 2000,
pagine: 171 - 179
SICI:
0014-4886(200003)162:1<171:EOSALD>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBRAL-ARTERY OCCLUSION; STRIATAL SPINY NEURONS; GLUTAMATE RELEASE INHIBITOR; PAIRED-PULSE FACILITATION; RAT HIPPOCAMPAL-NEURONS; LONG-TERM POTENTIATION; IIA NA+ CHANNELS; SYNAPTIC TRANSMISSION; CA2+ CHANNELS; NEOSTRIATAL NEURONS;
Keywords:
antiepileptic drugs; neuroprotective drugs; sodium currents; stroke; synaptic potentials;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Calabresi, P Univ Roma Tor Vergata, Dipartimento Neurosci, Neurol Clin, Via Tor Vergata135, I-00133 Rome, Italy Univ Roma Tor Vergata Via Tor Vergata135 Rome Italy I-00133
Citazione:
P. Calabresi et al., "Electrophysiology of sipatrigine: A lamotrigine derivative exhibiting neuroprotective effects", EXP NEUROL, 162(1), 2000, pp. 171-179

Abstract

Sipatrigine (BW619C89), a derivative of the antiepileptic agent lamotrigine, has potent neuroprotective properties in animal models of cerebral ischemia and head injury In the present study we investigated the electrophysiological effects of sipatrigine utilizing intracellular current-clamp recordings obtained from striatal spiny neurons in rat corticostriatal slices and whole-cell patch-clamp recordings in isolated striatal neurons. The number of action potentials produced in response to a depolarizing current pulse in the recorded neurons was reduced by sipatrigine (EC50 4.5 mu M). Althoughthis drug preferentially blocked action potentials in the last part of thedepolarizing current pulse, it also decreased the frequency of the first action potentials, Sipatrigne also inhibited tetrodotoxin-sensitive sodium (Na+) current recorded from isolated striatal neurons. The EC50 for this inhibitory action was 7 mu M at the holding potential (V-h) of -65 mV, but 16 mu M at V-h = -105, suggesting a dependence of this pharmacological effect on the membrane potential. Moreover, although the inhibitory action of sipatrigine on Na+ currents was maximal during high-frequency activation (20 Hz), it could also be detected at low frequencies, The amplitude of excitatory postsynaptic potentials (EPSPs), recorded following stimulation of the corticostriatal pathway, was depressed by sipatrigine (EC50 2 mu M). This inhibitory action, however, was incomplete; in fact maximal concentrations of this drug reduced EPSP amplitude by only 45%. Sipatrigine produced no increase in paired-pulse facilitation, suggesting that the modulation of a postsynaptic site was the main pharmacological effect of this agent, The inhibition of voltage-dependent Na+ channels exerted by sipatrigine might account for its depressant effects on both repetitive firing discharge and corticostriatal excitatory transmission, The modulation of Na+ channels described here, as well as the previously observed inhibition of high-voltage-activated calcium currents, might contribute to the neuroprotective efficacy exerted by this compound in experimental models of in vitro and in vivo ischemia. (C) 2000 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 07:56:29