title: An electrophysiological analysis of the protective effects of felbamate, lamotrigine, and lidocaine on the functional recovery from in vitro ischemia in rat neocortical slices.
abstract: We used field potential recording techniques to examine whether felbamate (FBM), lamotrigine (LTG), and lidocaine (LID) protect against the irreversible functional damage induced by transient ischemia. Five minutes of ischemia caused a depression of the field potential in rat cortical slices, which did not recover even after more than 1 h of washout. The N-methyl-D-aspartate (NMDA) antagonist ketamine (50 microM) protected against depression of the field caused by ischemia. On the other hand, the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2.3-dione (CNQX) (10 microM) had protective effects only if co-applied with ketamine. We found that either FBM (30-300 microM), which did not modify the amplitude of the field EPSP, or LTG (10-300 microM), which reversibly depressed the excitatory synaptic transmission, had a marked protective effect when superfused before and during the ischemic insult. After FBM (100 microM) and LTG (100 microM), the field EPSP recovered by 84 +/- 1% and 73 +/- 2.7% of control, respectively. Furthermore, LID (30-300 microM) was less effective than FBM and LTG in inducing a functional recovery from the damage caused by ischemia (58 +/- 1.8%). The rank order of potency, based on the maximal protection caused by the three drugs, was FBM > LTG > LID. Our results suggest that a noticeable neuroprotection can be obtained during glucose and O2 deprivation by preventive therapeutic regimens which use the two recently marketed anticonvulsant drugs, FBM and LTG.
authors.affiliation: IRCCS Santa Lucia, Clinica Neurologica Università di Roma Tor Vergata, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Siniscalchi
authors.forename: C
authors.initials: C
authors.lastname: Zona
authors.forename: E
authors.initials: E
authors.lastname: Guatteo
authors.forename: N B
authors.initials: NB
authors.lastname: Mercuri
authors.forename: G
authors.initials: G
authors.lastname: Bernardi
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects*; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000078328:Felbamate; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology*; D000077213:Lamotrigine; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014227:Triazines / Q000494:pharmacology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D011409:Propylene Glycols; D014227:Triazines; D008012:Lidocaine; D000077213:Lamotrigine; D000078328:Felbamate