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

EA Gelfuso, JL Liberato, AOS Cunha, MR Mortari… - Neuroscience …, 2013 - Elsevier
Neuroscience letters, 2013Elsevier
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 48h in the dose of 33mg/kg; ip, that is sufficient to induce fully kindled
seizures in saline icv treated rats in a short period of time (28 days). Treatments in two types …
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 48h in the dose of 33mg/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 (2mg/kg; i.p.) or i.c.v. injections of NA (12μg/μL), while in experimental groups in daily i.c.v. injections of different doses of Parawixin2 (0.15; 0.075; 0.015μg/μL). 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.
Elsevier