title: Lamotrigine and remacemide protect striatal neurons against in vitro ischemia: an electrophysiological study.
abstract: In the present study, we investigated the cellular and synaptic mechanisms underlying the neuroprotective action of lamotrigine and remacemide. Both drugs, in fact, have been reported to exert a neuroprotective action in in vivo animal models of ischemia. To address this issue, electrophysiological recordings and cell swelling measurements were performed from striatal neurons in control condition and during combined oxygen and glucose deprivation (in vitro ischemia) in a brain slice preparation. Lamotrigine, remacemide, and the active desglycinyl metabolite of remacemide, D-REMA, induced a concentration-dependent reduction of both repetitive firing discharge and excitatory postsynaptic potentials. However, while remacemide and D-REMA exerted their inhibitory action on glutamatergic transmission by blocking NMDA receptors, lamotrigine exerted a preferential presynaptic action, as indicated by its ability to increase paired-pulse facilitation. Both remacemide and lamotrigine were found to be neuroprotective against the irreversible field potential loss and cell swelling induced by in vitro ischemia, and coadministration of low concentrations of these drugs exerted an additive neuroprotective action. A combined use of lamotrigine and remacemide could be employed in clinical trials to enhance neuroprotection in neurological disorders involving an abnormal striatal glutamatergic transmission.
authors.affiliation: Clinica Neurologica, Dipartimento di Neuroscienze, Università di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. calabre@uniroma2.it
authors.forename: P
authors.initials: P
authors.lastname: Calabresi
authors.forename: M
authors.initials: M
authors.lastname: Marti
authors.forename: B
authors.initials: B
authors.lastname: Picconi
authors.forename: E
authors.initials: E
authors.lastname: Saulle
authors.forename: C
authors.initials: C
authors.lastname: Costa
authors.forename: D
authors.initials: D
authors.lastname: Centonze
authors.forename: F
authors.initials: F
authors.lastname: Pisani
authors.forename: G
authors.initials: G
authors.lastname: Bernardi
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015687:Cell Hypoxia / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004558:Electric Stimulation; D004594:Electrophysiology; D018846:Excitatory Amino Acids / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D066298:In Vitro Techniques; D000077213:Lamotrigine; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D014227:Triazines / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D018846:Excitatory Amino Acids; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D014227:Triazines; C067553:remacemide; D005947:Glucose; D000077213:Lamotrigine