N-ethyl lidocaine (QX-314) protects striatal neurons against ischemia: an in vitro electrophysiological study.
In this study, we have investigated the neuroprotective actions of the membrane impermeable, lidocaine analog, N-ethyl lidocaine (QX-314) in the striatum. The effects of this drug were compared with those caused by the strictly-related-compound and sodium channel blocker lidocaine. To address this issue, electrophysiological recordings were performed in striatal slices, in control condition (normoxia) and during combined oxygen and glucose deprivation (in vitro ischemia). Either QX-314 or lidocaine induced, to some extent, a protection of the permanent electrophysiological alteration (field potential loss) caused by a period (12 min) of ischemia. Thus, both compounds permitted a partial recovery of the ischemic depression of the corticostriatal transmission and reduced the amplitude of the ischemic depolarization in medium spiny neurons. However, while QX-314, at the effective concentration of 100 microM, slightly reduced the amplitude of the excitatory field potential and did not affect the current-evoked spikes discharge of medium spiny striatal neurons, equimolar lidocaine depressed the field potential and eliminated repetitive spikes on a depolarizing step. On the basis of these observations, our results suggest the use of QX-314 as a neuroprotective agent in ischemic brain disorders.
Laboratory of Experimental Neurology, Fondazione Santa Lucia IRCCS, Rome, Italy.
Marta
M
Armogida
Michela
M
Giustizieri
Cristina
C
Zona
Silvia
S
Piccirilli
Robert
R
Nisticò
Nicola B
NB
Mercuri
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015687:Cell Hypoxia / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency; D066298:In Vitro Techniques; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008839:Microelectrodes; D017072:Neostriatum / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology
D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; C012647:QX-314; D008012:Lidocaine; D012964:Sodium; D005947:Glucose