title: Traxoprodil decreases pentylenetetrazol-induced seizures.
abstract: Polyamines, including spermidine, facilitate seizures by positively modulating N-methyl-d-aspartate receptors (NMDAr). Although NMDAr antagonists decrease seizures, it remains to be determined whether traxoprodil, a selective antagonist at the NR2B subunit of the NMDAr, decreases seizures and whether spermidine facilitates pentylenetetrazol (PTZ)-induced seizures. Adult male Wistar rats were injected in the lateral ventricle with 0.9% NaCl (1μl, i.c.v.), spermidine (0.02, 0.2 or 2nmol/site, i.c.v.) or traxoprodil (0.2, 2 or 20nmol, i.c.v.) and with PTZ (35 or 70mg/kg, i.p.). The effect of orally administered traxoprodil (60mg/kg, p.o.) on seizures was also investigated. Latencies to clonic and generalized seizures, as well the total time spent in seizures were recorded by behavioral and electrographic methods (EEG). Spermidine (2nmol/site; i.c.v.) facilitated the seizures induced by a sub-threshold dose of PTZ (35mg/kg; i.p.), but did not alter seizure activity induced by a convulsant dose of PTZ (70mg/kg; i.p.). Traxoprodil (20nmol i.c.v.) increased the latency to generalized tonic-clonic seizures induced by PTZ (70mg/kg; i.p.). Traxoprodil (60mg/kg, p.o.) increased the latency to clonic and generalized seizures, and decreased the total time spent in seizures. These results support the role for the NR2B subunit in PTZ-induced seizures.
authors.affiliation: Department of Physiology and Pharmacology, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Naspolini
authors.forename: Ariane Rubin
authors.initials: AR
authors.lastname: Cocco
authors.forename: Felipe
authors.initials: F
authors.lastname: Villa Martignoni
authors.forename: Mauro Schneider
authors.initials: MS
authors.lastname: Oliveira
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Furian
authors.forename: Leonardo Magno
authors.initials: LM
authors.lastname: Rambo
authors.forename: Maribel Antonello
authors.initials: MA
authors.lastname: Rubin
authors.forename: Susan
authors.initials: S
authors.lastname: Barron
authors.forename: Carlos Fernando
authors.initials: CF
authors.lastname: Mello
mesh_terms: D000818:Animals; D008297:Male; D010433:Pentylenetetrazole / Q000633:toxicity*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C095106:traxoprodil mesylate; D010433:Pentylenetetrazole