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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Parawixin2, a novel non-selective GABA uptake inhibitor from Parawixia bistriata spider venom, inhibits pentylenetetrazole-induced chemical kindling in rats.

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Author(s):
Gelfuso, Erica A. [1] ; Liberato, Jose L. [1, 2] ; Cunha, Alexandra O. S. [1] ; Mortari, Marcia R. [3] ; Beleboni, Rene O. [4] ; Lopes, Norberto P. [5] ; dos Santos, Wagner F. [1, 2]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Dept Biol, Coll Philosophy Sci & Literature Ribeirao Preto, Neurobiol & Venoms Lab, BR-14049 Ribeirao Preto, SP - Brazil
[2] Neurosci & Behav Inst INeC, Ribeirao Preto, SP - Brazil
[3] Univ Brasilia, Inst Biol Sci, Brasilia, DF - Brazil
[4] Univ Ribeirao Preto, Dept Biotechnol, Ribeirao Preto, SP - Brazil
[5] Univ Sao Paulo, Coll Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, Organ Chem Lab, BR-14049 Ribeirao Preto, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Neuroscience Letters; v. 543, p. 12-16, MAY 24 2013.
Web of Science Citations: 11
Abstract

The aims of the present work were to investigate the effects of the repeated administration of Parawixin2 (2-amino-5-ureidopentanamide; formerly FrPbAII), a novel GABA and glycine uptake inhibitor, in rats submitted to PTZ-induced kindling. Wistar rats were randomly divided in groups (n= 6-8) for different treatments. Systemic injections of PTZ were administered every 48 h in the dose of 33 mg/kg; i.p., that is sufficient to induce fully kindled seizures in saline i.c.v. treated rats in a short period of time (28 days). Treatments in two types of positive controls (diazepam - DZP and nipecotic acid - NA groups) consisted in daily systemic injections of DZP (2 mg/kg; i.p.) or i.c.v. injections of NA (12 mu g/mu L), while in experimental groups in daily i.c.v. injections of different doses of Parawixin2 (0.15; 0.075; 0.015 mu g/mu L). Seizures were analyzed using the Lamberty \& Klitgaard score and kindling was considered as established after at least three consecutive seizures of score 4 or 5. Cumulative seizure scores for each group were analyzed using repeated measures of ANOVA followed by Tukey test. PTZ induced 4 and 5-score seizures after 12 injections in saline treated rats, whereas daily injection of Parawixin2 inhibited the onset of seizures in a dose dependent manner. Also, the challenging administration of PTZ did not raise seizure score in animals treated with the highest dose of Parawixin2 or those treated with DZP or NA. These findings together with previous data from our laboratory show that Parawixin2 could be a useful probe to design new antiepileptic drugs. (C) 2013 Elsevier Ireland Ltd. All rights reserved. (AU)